University Of California, San Diego

NIH Research Projects · FY 2025 · 1998-10

ABSTRACT Mammalian cells exhibit a precise gene regulation process, during which enhancers mediate rapid gene activation programs in response to different signals and ligands. While many principles of chromosomal mechanisms underlying enhancer functions have been deduced in the 39 years since their initial discovery, striking gaps in our knowledge remain. These include actions of a series of previously unknown, but required, enhancer-recruited complexes; contributions of physicochemical properties of enhancer condensates formed on the estrogen receptor  (ER) in signaling-dependent regulation; and the potentially important roles of interactions with subnuclear architectural structures. Further, because global genomic methods determine epigenomic events at only a single point in time, another striking gap in our knowledge is understanding the temporal principles underlying regulation of regulated transcriptional programs. Under physiological conditions, many signals present as a continuum from acute to chronic stimulation; however, the mechanistic and functional distinctions between acute and chronic enhancer activation remain poorly understood. Here, we take advantage of our knowledge of gene transcriptional control by nuclear receptors, exemplified by estrogen 17β-estradiol (E2)- dependent activation of transcriptional programs to address these basic questions. The central challenge in this competitive renewal is to provide a unified molecular logic that mechanistically links a series of required, but overlooked, components of signal-dependent enhancer activation strategies that underlie acute and chronic regulated gene expression programs. We will initiate a comprehensive investigation of new dynamic enhancer complexes and their interactions with the subnuclear architectural structures critically regulating transcription. These include the function of promoter antisense transcripts in promoter pause-release regulation; investigation of required contributions of Ku70 homodimers reading the TopoisomerseI:DNA covalent intermediate to assemble a new complex required for promoter pausing and enhancer activation events. We will investigate whether short sequences and specific amino acids in the ERN-terminal IDR mediate assembly of key RNP condensate components required for robust activation, including an unexpected role of KAP1 in these activation events. We will establish real time, multicolor imaging to uncover the dynamics of activated enhancer interactions, enhancer bursting events and relationship of activation to interactions with subnuclear architectural structures. We will explore the hypothesis that the most robust eRNA:protein enhancer condensates form a homotypic enhancer network resulting in cooperative activation of a subset of similarly activated homotypic enhancers separated by multiple TADs or even located on other chromosomes, properties are lost following chronic signal/ligand activation. These approaches will be complemented by alternative approaches for defining the dynamics of interactions between enhancers and subnuclear architectural structures. Our goal is to provide novel insights into regulated enhancer and promoter activation mechanisms.

NIH Research Projects · FY 2025 · 1998-05

Abstract This is a revised competitive renewal application for a NIH R01 grant entitled “Structures and Interactions of Chemokine Receptors” that has been continuously funded and very successful for 22 years. The long- standing goals of this project are to understand the mechanisms of chemokines and their receptors in various pathologies and to translate this information into the development of new intervention strategies. During the past funding period, we have made significant progress toward these goals. Specifically, we have de novo designed and chemically synthesized novel agonist molecules of CXCR4 receptor and completed a series of studies to characterize their in vitro and in vivo biological activities in eliciting site-specific migration and distribution of human neural stem cells and exerting significant and selective therapeutic effect in mice with neurodegenerative disease. The molecular mechanisms of action of these agents have been analyzed with a panel of point mutations at 24 residues located in each of the seven transmembrane domains of CXCR4 to map critical sites for CXCR4-agonist recognition and signaling. To further advance these peptide agonists toward potential therapeutics, we have developed a new strategy for peptide optimization with a small molecule mimicry approach. A novel small molecule with potent biological activity in itself has been discovered to mimic and to replace a large portion of the peptide agonist, resulting in a new prototype small molecule- peptide conjugate agonist with much higher CXCR4 affinity, smaller size, and lower synthetic cost that are advantageous for therapeutic development in the new grant period. These exciting discoveries and results have laid a solid foundation for continuing translational research in regenerative medicine and basic research to understand the mechanisms underlining stem cell migration and signaling.

NIH Research Projects · FY 2026 · 1997-04

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. The mission of the San Diego Center for AIDS Research (SD CFAR) is to drive HIV discoveries and advance cutting-edge research by San Diego investigators to improve the lives of people with HIV and to stop new infections. Our Center’s research priorities are aligned with the NIH Office of AIDS Research priorities and include preventing new infections, optimizing HIV care, and developing a cure, while promoting health service reach for people with and at risk for HIV. The specific aims of the SD CFAR are to: 1. Accelerate the pace of discovery by providing the foundation for productive collaborations across fields, investigators, member institutions, and the HIV community. 2. Capitalize on our public engagement and partnerships to develop long-lasting research programs that can inform policy, practice, and implementation. 3. Provide Training, Inspiration, Mentoring, and Expert guidance (TIME) to local and collaborating investigators across career stages. 4. Provide scientific and administrative leadership to CFAR member institutions, investigators, and across our region. Structure: The SD CFAR is multi-institutional, with members at La Jolla Institute of Allergy and Immunology (LJI), San Diego State University (SDSU), Scripps Research (SR), and University of California San Diego (UCSD). The Center is co-directed by members of our Operations Team including Drs. Davey Smith (contact PI), Douglas Richman, Sonia Jain, Dennis Burton, and Jamila Stockman (Leadership Trainee). Our CFAR is comprised of seven Cores and one Scientific Working Group. We continue to be guided by our Advisory Committees, as well as our Co-Directors, Core Directors, Scientific Working Groups, and our membership. Progress: Since our renewal in 2017, SD CFAR efforts have yielded a productive and growing group of investigators whose research work extends from cellular restriction factors that impede HIV replication and transmission to behavioral approaches to improve prevention and treatment. Our funded research base remained at Tier 3 status and steadily increased by $11.9M between FY18 - 21. Further, there have been 870 CFAR-supported publications this past cycle, representing a 44.5% increase since the last renewal. We remain committed to supporting catalytic multidisciplinary research, bringing breakthroughs from laboratory bench to patient bedside, while fostering a new generation of innovative, independent investigators.

NIH Research Projects · FY 2024 · 1997-01

HMG-CoA reductase (HMGR) is a key enzyme of the sterol pathway. HMGR undergoes feedback- regulated degradation conserved from yeast to humans. We exploit this conservation to understand the machinery and mechanisms at play in regulated degradation of the yeast Hmg2 isozyme. Degradation occurs by the HRD ER-associated degradation (ERAD) quality control pathway, also responsible for the degradation of misfolded ER proteins. Hmg2 ERAD is regulated by sterol pathway molecule GGPP. GGPP accomplishes control by causing reversible misfolding that triggers HRD pathway degradation. GGPP’s action on Hmg2 has many features of allosteric control; we have named this type of regulation “mallostery” to combine the ideas of misfolding and allostery. In the proposed studies we will unravel the mallosteric regulation of Hmg2, to better understand sterol pathway control, and for the high potential mallostery holds as broadly applicable avenue of drug discovery. Specifically, we will : 1) Study the features of Hmg2 that allow GGPP-dependent reversible misfolding: GGPP’s effect on the Hmg2 transmembrane regions is highly specific, and requires the broadly conserved sterol sensing domain (SSD). We will discover the sequence features of Hmg2 responsible for mallosteric control by GGPP, investigating the role of known Hmg2 motifs and discovering sequence features with unbiased genetic approaches; 2) Explore the mechanism of GGPP dependent regulation of Hmg2- We will test the hypothesis that GGPP is a high potency ligand for Hmg2, causing reversible misfolding through development of direct interaction assays, analysis of GGPP analogues, and through in vitro reconstitution of regulated ubiquitination of Hmg2 using a number tools and approaches developed in the last funding cycle; and 3) Discover the role of INSIG proteins in GGPP-mediated misfolding of Hmg2- The INSIG proteins are critical in mammalian lipid homeostasis, and are conserved in yeast (Nsg1 and 2). As in mammals, yeast INSIGs function by transducing sterol signals. Yeast INSIG controls GGPP-dependent Hmg2 misfolding in a manner dependent on the biosynthetic sterol lanosterol. Thus the yeast INSIGs impose a second layer of regulation on mallosteric regulation by GGPP. We will use the tools, mutants, and methods from both the previous funding period, and the above studies to explore the mechanism and physiology INSIG function in Hmg2 regulated stability. We will also execute a genetic screen to glean the broader biology of INSIGs, about which almost nothing is known despite the key and highly conserved roles of these proteins in human lipid homeostasis and pathology.

NIH Research Projects · FY 2026 · 1996-07

PROJECT SUMMARY/ABSTRACT - OVERALL Founded in 1977 as the only NCI-designated Comprehensive Cancer Center in San Diego County, the mission of the Moores Cancer Center (MCC) is to reduce the impact of cancer in the region and beyond by fostering scientific discovery, research training, and interdisciplinary care. MCC’s goal is to create, translate, and deliver high-impact discoveries and innovations in cancer prevention and care to its patients, through a deep understanding of the needs of the catchment area, and to prepare the next generation of cancer researchers. MCC’s aims are to: Aim 1) Reduce cancer burden in the MCC catchment area by focusing research on early detection, prevention, diagnostics, therapeutics, and survivorship, along with community outreach efforts; Aim 2) Leverage MCC strengths across the consortium with local community assets and partnerships to develop and test innovative preventive, diagnostic, and therapeutic approaches in cancer patients and those at risk; and Aim 3) Provide training and education across the continuum. To this end, MCC brings together 337 members from 12 Schools and 40 Departments, from UCSD and two consortium partners, San Diego State University and La Jolla Institute for Immunology. Furthermore, MCC integrates the resources of UCSD Health Sciences and its affiliated hospitals for a unified approach to cancer research and clinical care. MCC fulfills its mission through the activities of its five Research Programs: Cancer Biology and Signaling, Cancer Control, Hematological Malignancies, Structural and Functional Genomics, and Solid Tumor Therapeutics. The Programs are supported by eight Shared Resources (Biostatistics, Biorepository and Tissue Technology, Flow Cytometry, Genomics and Computational Biology, In Vivo, Microscopy, Population Science, and Transgenic Mouse) with infrastructure and expertise provided by Community Outreach and Engagement, Cancer Research Training and Education, Clinical Protocol and Data Management, and Protocol Review and Monitoring. The Moores Cancer Center, led by Director Dr. Diane M. Simeone, has made impactful progress over the grant period compared to the prior funding period. MCC members authored 5,035 cancer-relevant research articles (28% increase), and in 2024 were supported by $41.4M (DC) in annual NCI funding (55% increase), with a 29% increase in total cancer-relevant funding. The number of NCI team science grants increased from 33 to 59 (79% increase). The number of patients enrolled in MCC interventional treatment trials increased from 573 at the last submission, to an annualized projection of 660 in CY 2025; and the median time to activation declined from 224 days in 2018 to 86.5 days in April 2025. Total space under MCC Director’s control grew by 31%; three new Senior Leadership positions have been added to more optimally position the MCC as a highly translational consortium cancer center; and a new 2024-2029 Strategic Plan was created to guide the MCC over the next grant period. MCC will continue its trajectory of driving highly innovative research and clinical care embedded in a culture of collaboration.

NIH Research Projects · FY 2025 · 1995-09

PROJECT SUMMARY The Cancer Biology, Informatics & Omics (CBIO) program at the University of California, San Diego Health Sciences (UCSDHS) trains PhD students and post-doctoral scholars in cancer research that emphasizes discovery and application/development of informatics tools and omics technologies. The design of CBIO training is driven by three rationales: (i) Basic research discoveries are essential to advancements in cancer diagnosis and treatment; (ii) Cancer omics data combined with model organism research have accelerated the discovery and analysis of novel cancer genes and pathways; and (iii) Investigation of cancer biology in the human system requires proficiency in omics technologies and computational tools. The duration of each trainee appointment is for two-years with the goal to (a) foster research excellence in advanced systems and approaches, (b) provide foundational knowledge in cancer biology and bioinformatics, (c) develop translational insights through Tumor Boards at the Moores UCSD Cancer Center, (d) keep pace with cancer research advancements through journal clubs, seminars, workshops, and national conferences, (e) uphold scientific ethics, rigor and reproducibility through coursework, workshops, refreshers and reinforcements, (f) develop trainee professional careers through coursework, workshops and annual updates of myIDP plans, and (g) promote a collaborative community through monthly scientific meetings and annual retreats. The CBIO program faculty conduct cancer research with demonstrated productivity and expertise in diverse experimental systems. Besides biologists, biochemists and geneticists, our faculty also include mathematicians and computer scientists working on the leading edge of computational cancer research. CBIO faculty are held to the highest scientific standard and our senior faculty each has a strong track record in training graduate students and postdoctoral scholars. CBIO and its predecessor has had a successful track record in mentoring junior faculty, who bring new research and teaching expertise to the program. CBIO has appointed 10 predocs/9 postdocs using the 3 predoc/3 postdoc slots awarded each year and propose a continuation of 3 funded predoc and 3 funded postdoc positions in the next funding cycle. CBIO trainees are PhD students and postdoctoral scholars with outstanding academic records and cancer-focused research projects, selected from large pools of highly qualified candidates. The majority of our former trainees are conducting research in academia, biotech, and pharmaceutical companies with others pursuing careers in teaching, scientific writing and clinical practice. An Executive Committee of CBIO selects and evaluates trainees and faculty with annual input from our External and Internal Advisory Committees. CBIO has added value to research and education at UCSDHS by offering a new Cancer Genomics journal club, by organizing a new training area on Computational Biology and Data Science in the Biomedical Sciences graduate program, and by catalyzing collaborative research leading to new shared grant funding. Building on these successes, CBIO will continue to serve as a hub for big data cancer research and education at UCSDHS in the years to come.

NIH Research Projects · FY 2024 · 1994-09

This T32 training program with 4 post-doctoral trainees/year has been funded by NIAID since 1994 and takes advantage of the combined extensive allergy research activities in the La Jolla scientific community. The faculty members are from two neighboring institutes: University of California, San Diego (UCSD), and the La Jolla Institute for Allergy and Immunology (LJI) both located on the UCSD campus and both UCSD faculty. The program is open to MD's and Ph.D.'s interested in allergic/immunologic disease-oriented research and committed to a career in basic research applied to these clinical diseases. The trainees have opportunities to be exposed to a wide range of allergy research topics. In addition, the inter-institutional training program serves as a catalyst for promoting interactions and collaborations among researchers from different institutes. All 23 faculty members have well established NIH funded research programs; their research backgrounds are diverse and when taken together encompass allergy, immunology, biochemistry, cell biology, molecular biology, bioinformatics, genetics, epigenetics, and the microbiome. Therefore, this training program represents an interdisciplinary approach. The trainees can be involved in the following research areas: 1) genetics and epigenetics, 2) biology of inflammatory cells, including mast cells, and eosinophils; 3) T cells; 4) dendritic cells, 5) innate immune responses (TLRs, ILC2, NK cells) 6) cell receptors critically involved in allergic reactions; 7) signal transduction; 8) inflammatory mediators/cytokines; 9) functions of epithelial cells; 10) complement, and 11) endothelial adhesion. The goals of the program are 1) to foster the development of trainee's laboratory based investigative skills, in particular, applying molecular and cellular biological approaches to study mechanisms of allergic diseases, and 2) to mentor trainees to successfully compete for either independent research grants and faculty positions, or research positions in biotechnology. The trainees are expected to devote over 90% effort to research, and training will be supplemented by conferences, seminars, journal clubs and courses. Upon completion of the program trainees will have developed a solid background in the molecular and cellular mechanisms of allergic inflammation and become qualified and confident in embarking upon their careers as independent investigators in allergy research.

NIH Research Projects · FY 2025 · 1994-09

This is an application for a 5-year renewal of the T32 Fellowship Program in Geriatric Mental Health at the University of California San Diego (UCSD). As the population ages, the demand for independent investigators in geriatric mental health will continue to increase. Over the last 15 years, we have trained 38 postdoctoral Fellows and 12 predoctoral Fellows. This T32 program, continuously funded since 1994, is part of a larger research training environment within UCSD’s Division of Geriatric Psychiatry and Department of Geriatric Psychiatry. It is also affiliated with the UCSD Center for Healthy Aging, Sam and Rose Stein Institute for Research on Aging, and UCSD’s Clinical and Translational Science Award (CTSA). Since our last renewal, 69% of our T32 trainees have been women, 35% have been from racial/ethnic minority groups, and 23% have been from underrepresented groups (based on race/ethnicity, disability, or disadvantaged backgrounds, per the NIH definition). 96% completed at least two years of Fellowship training or are still in training, and 100% are continuing in full-time research activities. All trainees with at least one year in the program have published multiple peer-reviewed papers. Our postdoctoral trainees have obtained 5 K awards or VA Career Development Awards since our last renewal. Previous predoctoral and postdoctoral Fellows have obtained funding from NIH, VA, and various foundations. We place major emphasis on career development, both for mentees and mentors. The Fellowship program includes individual mentoring along with experiential training in team science, complemented by didactic activities. A personalized Individual Development Plan (IDP) is created with each trainee early in the course of the Fellowship. Writing and statistical skills enhancement, guidance on balancing personal and professional obligations, and exposure to cross-disciplinary co-mentors and collaborators characterize our program. This renewal application proposes to support 5 postdoctoral Fellows and 2 predoctoral Fellows (in clinical psychology or neuroscience) annually. Over the next 5 years, we will continue to focus on technology in aging and mental health, including mobile health and data science technologies to improve assessment, treatment, and service delivery for older adults with psychiatric illnesses. We will also continue to emphasize clinical trials, mechanistic research, translational and basic neuroscience, implementation science, data science, physician and pharmacist scientists, and diversity of trainees. In all efforts, we will prioritize research of high public health significance (e.g., focusing on reducing disability and improving functional outcomes and quality of life). We have developed a strong plan for evaluation of the training process including short-term and long-term outcomes, including research productivity for Fellows and professional advancement for mentors.

NIH Research Projects · FY 2024 · 1994-08

Project Summary/Abstract The emerging Hippo pathway plays a major role in development, cell growth, tissue homeostasis, and organ size. Dysregulation of Hippo pathway contributes to human diseases, most notably cancer. TCGA study with analysis of over nine thousand human tumor samples has revealed that Hippo is one of the nine signals pathways that are frequently altered and contributes to human cancer. The Hippo pathway consists a kinase cascade that phosphorylates and inhibits the downstream transcription module of YAP/TAZ. A wide range of signals have been discovered to modulate the Hippo pathway. However, the precise mechanism of Hippo pathway regulation, particularly how upstream signals feed into the Hippo kinase cascade, is largely unknown. The major goal of this proposal is to understand the fundamental mechanism of Hippo pathway regulation. By screening for natural compounds to modulate the Hippo pathway, we have discovered that microcolin B (MCB) potently activates the Hippo kinases. Our preliminary study indicates that MCB directly targets phosphatidylinositol transfer protein (PITP) to activate the Hippo pathway. PITP functions to transfer phosphatidylinositol from ER, the site of synthesis, to other compartment membranes, particularly plasma membrane, in the cell. Our preliminary data suggest an exciting and novel model that phosphatidylinositol metabolites play a key role in Hippo regulation. We further propose that NF2, which is a key upstream regulator of the Hippo pathway and can bind phosphatidylinositol phosphates (PIPs), may mediate the PIP signal to Hippo regulation. This proposal aims to demonstrate the function and mechanism of phosphatidylinositol and its metabolites in Hippo regulation and how PIPs mediate upstream signals to Hippo. Further, completion of this project will provide exciting scientific basis of using small molecules to target the Hippo pathway for YAP dependent cancer.

NIH Research Projects · FY 2025 · 1993-03

PROJECT SUMMARY/ABSTRACT: This proposal represents a continuation of a training program at UC San Diego in the Contemporary approaches in cancer cell signaling and communication, requesting funding for Years 34-38. All faculty mentors are members of the Moores UCSD Cancer Center, with appointments in Chemistry & Biochemistry, Bioengineering, Biological Sciences, or the School of Medicine. Our program also incorporates faculty from the Salk Institute. Training faculty include 5 members of the National Academy of Sciences, 3 Fellows of the AACR, and 1 Lasker recipient. Faculty mentors are organized into three broad research areas: 1) Biochemistry of tumor cell signaling; 2) Cell plasticity and tumor microenvironment; 3) Engineering approaches to cell signaling and communication. Training involves a monthly Training Grant Seminar with two presentations by trainees, formal courses, journal clubs, trainee/faculty luncheons, and events to promote program cohesion. A Supervisory Committee provides strong program oversight in trainee selection, evaluation, and programmatic decisions, continuing unchanged from the past 5 years. With this submission, program leadership envisions continued vibrancy for our program with the inclusion as the lead PD/PI for Years 34-38 of Prof. Jing Yang, a mid-career expert in tumor metastasis, who will strengthen our leadership team with her commitment to training and mentoring in cancer biology. Overall, this program remains highly dynamic, synergistic, and interdisciplinary. TRAINEES: Current and past trainees have excellent records of research accomplishments. We have requested 6 postdoctoral positions and 4 predoctoral positions for Years 34-38, unchanged from present. The requested slots continue to be justified by ongoing growth at UC San Diego, by the ability of the training faculty to recruit outstanding trainees to their labs, and by the interactive nature of the training labs that collectively provide a superb training environment. Predoctoral trainees are drawn from graduate students accepted into Chemistry & Biochemistry, Bioengineering, or Biological Sciences, and are appointed typically for 2 years. Postdoctoral trainees are selected from postdoctoral candidates applying for positions in the laboratories of the training faculty, and appointed for a maximum of 2 years. Trainees accepted into our program are expected to have strong backgrounds in chemistry, biochemistry, bioengineering, and molecular and cell biology. All trainees are expected to publish first-author publications and encouraged to apply for independent fellowships. PROGRAM HIGHLIGHTS AND CHANGES: This renewal highlights several changes, including: eight exciting new faculty additions, strengthened interactions with the Moores UCSD Cancer Center; greater faculty/trainee interactions to promote program cohesion; strong support from five members of our External Advisory Board; compelling letters of support from members of our supervisory committee; and strong endorsements and commitments of support from key administrative leaders.

NIH Research Projects · FY 2025 · 1991-04

Liver X receptors (LXRs) a and b are members of the steroid and thyroid hormone receptor superfamily of ligand- dependent transcription factors that regulate lipid metabolism and inflammation in macrophages and other cell types. Synthetic ligands that activate LXRs have been shown to have protective effects in mouse models of cardiovascular, metabolic and neurodegenerative diseases. However, nearly all synthetic LXR agonists developed to date cause unacceptable levels of steatosis and hypertriglyceridemia due to on target induction of the Srebp1c gene in hepatocytes, preventing their clinical application. Studies in our laboratory identified desmosterol as the dominant endogenous LXR agonist in mouse macrophage foam cells and in human atherosclerotic lesions and provided evidence that hepatocyte derived desmosterol regulates Kupffer cell LXR activity in response to a steatosis-inducing diet. Our evaluation of desmosterol and synthetic desmosterol mimetics indicate that they can activate LXR target genes in macrophages without inducing Srebp1c expression in hepatocytes. The mechanistic basis for these effects is unknown, but these observations have significant implications for the understanding of cell specific regulation of LXR target genes in homeostasis and disease and suggest a path towards the development of physiologically inspired agonists for therapeutic applications. A major knowledge gap limiting understanding of LXR biology is that nearly all systematic in vivo studies of LXRs and LXR ligands have been performed in a single strain of mice; C57Bl/6. Our preliminary data reveals substantial differences in responses of different inbred strains of mice to a prototypic synthetic LXR agonist, supporting the hypothesis that a deep evaluation of the impact of natural genetic variation on LXR function in macrophages and hepatocytes will yield significant insights into mechanisms by which LXRs regulate lipid metabolism and inflammation in these two cell types. Studies proposed in Specific Aim 1 will directly evaluate this hypothesis. In addition, the transcriptomic and epigenetic data obtained in this aim will enable derivation of cell specific transcriptional networks mediating LXR-dependent gene expression in each cell type. Studies proposed in Specific Aim 2 will test the hypothesis that natural LXR agonists and synthetic analogues drive cell- and gene-specific responses in hepatocytes and macrophages at a genome wide level. Parallel studies in human and mouse macrophages and hepatocytes will establish similarities and differences across species. Studies proposed in Specific Aim 3 will investigate roles of transcriptional co-regulators in mediating these effects. Collectively, these studies will qualitatively advance understanding of mechanisms by which LXRs regulate gene expression that are likely to be relevant for understanding signal-dependent gene regulation in general and may also provide insights for development of LXR agonists that retain therapeutic efficacy in cardiovascular, metabolic and neurodegenerative diseases without unacceptable side effects.

NIH Research Projects · FY 2025 · 1990-08

PROJECT SUMMARY/ABSTRACT The sustained global impact of the viral pandemics of HIV and SARS-CoV-2 and the challenges to the management and prevention of disease require the training and development of talented new researchers. Since 1990, we trained postdoctoral scholars in this program at the University of California, San Diego (UCSD). The program is designed to produce new investigators who are capable of independently leading impactful research in basic and translational viral biology and pathogenesis. This application proposes renewal of this highly successful training program. Based on our strategic planning process, we propose an expansion in the program’s scope to better reflect the research priorities of the Office of AIDS Research and to respond to the challenges of viral pandemics like COVID-19. Specifically, the program’s priorities will include reducing incidence (including vaccination), therapeutics and cure, health disparities, and long-term comorbidities. To reflect this expansion, we propose a new leadership structure, have grown our faculty to 23 mentors who have an extensive history of independent research, collaborations, and training. We have renamed the application to reflect these changes, HIV and Other PandEmics, or HOPE. We have also added 10 mentors-in-development (MiDs), who are an internal talent pool from which a new generation of mid-career mentors for the HOPE Training Program will develop over time. The faculty are committed to identifying talented and committed postdoctoral trainees and to providing the environment and opportunities that will support their path to independence in medically relevant basic, translational, clinical, and epidemiological research. The program will retain its successful educational and training elements, while incorporating innovative new offerings to address one of the greatest challenges facing modern medicine and public health, SARS-CoV-2. The research interests and activities of our faculty support the evolving focus and priorities of virology research in general and specifically within our program. We propose to support six postdoctoral trainees for a training period of two to three years each. We aim to continue to improve on our success in training underrepresented minorities and women. Through our program of closely mentored, trainee-driven research, interactive research review, and career development activities, our overarching goal remains to prepare the next generation of scientists for highly productive careers in biomedical research with local, national and international impact.

NIH Research Projects · FY 2025 · 1990-05

We are excited, if presented with the opportunity, by the prospect of continuing over 3 decades of research into the mechanisms of peroxisome (PO) biogenesis. Our current work relies on yeast models, which have provided, and will continue to reveal, deep insights into this conserved and important biological process in humans, while also enhancing the diagnosis and understanding of the myriad of PO biogenesis disorders (PBDs). Our past work has centered on PO homeostasis, which balances the biogenesis and turnover processes, but we focus here on the birth of POs in cells that have no pre-existing POs, because previous genetic screens were done in cells that generate POs by redundant pathways involving both growth and division of pre-existing POs and de novo PO biogenesis. In doing so, redundant and essential genes were not identified, leaving a serious gap in our understanding. We remedy this using a novel, innovative, high-throughput screen (HTS) for PO biogenesis mutants in cells that are incapable of producing POs via growth and division. We show, using a pilot mini-screen, that unlike previous screens, our strategy is yielding putative hits in many steps of PO biogenesis, while identifying both known and novel genes, for the first time, including those involved in PO dynamics. This promising HTS platform, which we validate by proof-of-concept experiments, has provided a treasure trove of genes that now need deep investigation to understand how they function. Notably, many of the new genes we identified interact with known players we and others have been investigating, and a significant number are present at membrane contact sites (MCSs) between POs and other organelles. This presents a second fascinating avenue of pursuit, wherein we will probe the importance of metabolite (especially lipids) transport functions of the ER-PO MCSs. Our analyses will judiciously explore two yeast models to address evolutionary conservation and derive common, conserved principles. This leads naturally to the third, poorly-explored arena of interorganellar communication, for which we have found a novel, experimentally-tractable link, which is the requirement of mitochondrial redox and oxidative phosphorylation (OXPHOS) for PO proliferation (i.e. increase in PO number/cell). Thus, each of three new avenues of pursuit is expected to open new doors that will exceed what we alone can understand, but our long-term vision is to create interesting, new, community opportunities for future exploration in PO biology, knowing that it will be relevant, albeit indirectly, to patients with PBDs and the alleviation of their suffering. This proposal represents an expansion of scope by synergizing our molecular and cell biology efforts with the technical and intellectual prowess of the Aitchison laboratory (SCRI) and is backed by a significant track record of advances made by both PIs in PO biology. The Aims of our proposal are: Aim 1: Identify and perform functional studies on the machinery and regulators of de novo PO biogenesis. Aim 2: Elucidate how lipid regulators, MCSs and PO biogenesis proteins work together in ppV budding. Aim 3: Understand the role of mitochondrial signaling in the control of PO biogenesis.

NIH Research Projects · FY 2025 · 1989-04

Nuclear clearance and cytoplasmic aggregation of TDP-43 have been reported in almost every age-dependent neurodegenerative disease, including as the defining feature of a recently recognized dementia in the oldest of the elderly, an AD-like syndrome named Limbic-predominant Age-related TDP-43 Encephalopathy (LATE), a proportion of the hippocampal neurons in Alzheimer's disease (AD), >40% of frontal temporal dementia (FTD), and >90% of instances of ALS. Our prior efforts (for which we now seek renewed support) have established that transient stress can induce Liquid-Liquid Phase Separation (LLPS) of cytoplasmic TDP-43 into liquid droplets that then transition to a solid state, slowly deplete nuclear TDP-43, and provoke cell death over a timescale of weeks. We also determined that partial or complete proteasome inhibition (to mimic the established decline in proteosome activity during normal aging) provokes TDP-43 mislocalization/accumulation within the cytoplasm. Quantitative mass spectrometry (with proximity-labeling and isobaric-tagging) has identified the small heat shock protein HSPB1 to be a regulator of cytoplasmic TDP-43 phase separation and subsequent aggregation. HSPB1 partitions into TDP-43 droplets, inhibits TDP-43 assembly into fibrils, and mediates disassembly of stress-induced, TDP-43 droplets. Building on our prior and continuing work, we now propose to determine 1) how the age-dependent decrease in proteasome activity drives TDP-43 loss of function, cytoplasmic mislocalization, phase separation, and aggregation and 2) how protein chaperone HSPB1, in conjunction with HSP70, affects cytoplasmic TDP-43 phase separation, inhibits TDP-43 assembly into fibrils, and mediates disassembly of TDP-43 droplets. We have also initiated development of an approach to generate new/replacement neurons in the aged adult mouse brain by transiently suppressing the RNA binding protein Polypyrimidine Tract Binding Protein-1 (PTB) using an antisense oligonucleotide (ASO) delivered by a single injection into cerebral spinal fluid (CSF). Radial glial-like cells (and possibly other GFAP-expressing cells) convert into new neurons over a two month period, acquire mature neuronal character, and functionally integrate into endogenous circuits that modify mouse behavior. Here we will systematically identify the functionality, localization, cell origin, timing, and molecular pathways of cells undergoing identity conversion, with a primary assay the development and utilization of single cell RNA signatures obtained with spatial transcriptomics (Multiplexed Error-Robust Fluorescence In Situ Hybridization [MERFISH]).

NIH Research Projects · FY 2025 · 1988-07

PROJECT SUMMARY DNA mismatch repair (MMR) plays critical roles in eukaryotic cells including: 1) suppressing mutations that result from misincorportation errors during DNA replication that escape DNA polymerase proofreading; 2) suppressing mutations that result from misincorporation events that occur due to chemical modification of DNA or DNA precursors; 3) preventing genome rearrangements due to recombination between divergent DNA sequences; 4) correcting mispaired bases in recombination intermediates; and 5) detecting DNA damage and activating signaling pathways linked to cellular responses, including cell cycle control and cell death. Consequently, MMR defects cause increased rates of accumulating mutations and genome rearrangements resulting in a characteristic genome instability signature and resistance to killing by some DNA damaging agents. In humans, MMR defects underlie both inherited and sporadic cancers, cause tumors to become resistant to some chemotherapy agents and appear to cause quite striking sensitivity of cancers to immunotherapy. Thus, a better understanding of MMR pathways and the consequences of MMR defects will impact human health by: 1) informing our understanding of MMR status; and 2) guiding improvements in the development and use of therapies for MMR-deficient cancers. The proposed studies use Saccharomyces cerevisiae as a model system to study the mechanisms of the conserved eukaryotic MMR pathways. The following lines of investigation will be carried out: 1) genetic approaches will be used to study Msh2- and Mlh1-interacting proteins, identify new MMR proteins and study the activation of the Mlh1-Pms1 endonuclease; 2) reconstitution approaches will be used to study the MMR pathways in which mispair excision is mediated by either Exo1 or the Rad27 endonuclease focusing on mispair excision mechanisms, the recruitment of Exo1 and Rad27 to MMR reactions and whether DNA pol ε can act in Rad27-mediated MMR; 3) reconstitution approaches will be used to study MMR pathways that are dependent on the Mlh1-Pms1 endonuclease including pathways where Mlh1-Pms1 initiates mispair excision by Exo1 and Rad27 and a novel, newly reconstituted pathway where mispair excision is mediated only by Mlh1-Pms1; and, 4) individual steps in MMR reactions will be studied primarily by investigating the protein-protein interactions and higher order complexes of proteins that drive MMR using Surface Plasmon Resonance and single molecule biochemistry methods. The long-term goal of these studies is to develop a detailed understanding of the biochemical and molecular mechanisms of MMR and how cells utilize MMR to prevent mutations and genome rearrangements. Because MMR is highly conserved, the results from studies of S. cerevisiae MMR will provide insights into the mechanisms of MMR in human cells. Consequently, this project will provide insights that can be applied to understanding the genetics of human cancers and the biology of MMR defects in human cancers in addition to providing a basic understanding of MMR mechanisms.

NIH Research Projects · FY 2025 · 1986-07

Project Summary Neuroscience is among the fastest growing area of science and has produced remarkable developments that will have profound implications for the understanding and treatment of mental disorders. Innovations and advancements in molecular genetics, brain imaging methods, molecular biology and have resulted in unprecedented advances that have extended visions of understanding and treating psychiatric disorders to the hope of preventing and even curing them. However, there is still a gap in applying knowledge and tools to psychiatric disorders that is due, in part, to a shortage of clinical and translational-science researchers. Consequently, it is imperative train researchers to translate important basic science findings into clinically relevant treatments. This competitive renewal application requests continued NIMH funding for the long-standing, successful University of California, San Diego (UCSD) Fellowship in Biological Psychiatry and Neuroscience. The Fellowship is designed for provide education, research training, and career opportunities for 7 post-doctoral fellows with a particular emphasis on candidates that are focused on using biological tools to understand pathophysiology and brain processes of psychiatric illness and develop potential treatments for these disorders. The overall goal is to train fellows from diverse backgrounds to acquire the skills necessary for the conceptualization, planning, conduct and publication of research in biological psychiatry and neuroscience with the ultimate goal to become independent and funded researchers. Specific goals of the Fellowship are: (1) To recruit a diverse group of highly accomplished fellows for advanced research training (2) To provide a high level of training necessary for successful transition into an independent research career, which is focused on: a) Ethical conduct of research and research ethics; b) General methodologies applicable to research in biological psychiatry and neuroscience; c) Use of data science in research; d) Methods to improve reproducibility of results; e) Specific approaches relevant for the fellow's individual research project; f) Training in scientific writing directed at production of scientific papers and grant applications.; g) Grant writing skills and education regarding NIH procedures (3) To enable the fellow to conduct and complete a specific research project that can be viewed as a seed for an independent research career trajectory and includes: a) Proposal of a research project based on NIH forms and guidelines; b) Implementation of this project with a UCSD-affiliated mentor, and c) Regular monitoring and evaluation of research progress. (4) To provide practical advice and support for career development, which includes: a) Opportunities for fellows to present their projects and peer-review grant applications, and practice grant review as a mock reviewer through mandatory attendance of the weekly didactic session; b) Explicate milestones and career guidelines that are written in the T32 Individual Development Plan (IDP); c) Network with senior researchers within UCSD and other organizations, and via online resources; d) Fellows have regular one-on-one meetings with directors for scientific and career development related mentoring and support.

NIH Research Projects · FY 2025 · 1985-07

Project Summary The endoplasmic reticulum (ER) undergoes autophagic degradation in response to the accumulation of aggregated proteins within its lumen or in response to starvation. We have proposed that in yeast, actin assembly at sites of contact between the cortical ER (cER) and endocytic pits is required to displace elements of the cER from their association with the plasma membrane so that they can interact with the autophagosome assembly machinery near the vacuole. To test our model, we will determine if the requirement in cER-phagy for actin assembly at endocytic pits can be bypassed by deleting all six genes encoding ER-plasma membrane tethers (DTether). If the role of actin assembly is to push the cER away from the plasma membrane, the DTether mutations should bypass the need for actin assembly in ER-phagy. We will ask if the bypass of actin assembly is specific to cER-phagy or if actin-related defects in other selective autophagy pathways, such as nucleophagy, mitophagy, and pexophagy are also bypassed. As an additional test we will ask if an artificial ER-plasma membrane tether can block cER- phagy in both wild type and the DTether strain. Extensive parallels between ER-phagy in yeast and mammalian cells suggest a conserved mechanism. A long-term goal will be to use siRNA knock downs of actin assembly components in U2OS cells to assess their roles in ER-phagy. We will order all known cER-phagy requirements with respect to the displacement of the cER from the plasma membrane. Our recent data suggests that a vesicle coat adaptor protein associates with a selective ER-phagy receptor prior to the displacement of cER from the plasma membrane. We will develop a bimolecular fluorescence complementation assay to visualize the dynamics of this ER-phagy intermediate in live cells. We will also order the displacement of the cER from the plasma membrane with respect to the super assembly of Atg40 oligomers, a process required for packaging of ER fragments into autophagosomes. We will explore a novel fluorescence complementation assay for super assembly of Atg40 oligomers that will allow visualization in live cells. In total our studies will define the pathway by which the ER is degraded by autophagy. This pathway plays a key role in a variety of human diseases including neurodegenerative disorders and forms of diabetes.

NIH Research Projects · FY 2025 · 1979-07

Project Summary Abstract This proposal is a resubmission of a renewal application that has been supported by NHLBI for nearly four decades. Support for eight postdoctoral trainee positions is requested in this renewal application, as has been present during the current funding period. The overriding goal of our program remains to provide the highest caliber training of postdoctoral trainee scientists and physician-scientists, to build the pipeline of tomorrow’s cardiovascular researchers. Our trainees are instilled with expertise so that they can solve cardiovascular problems using multidisciplinary approaches, as they are mentored by the excellent faculty at University of California, San Diego (UCSD), one of the top research institutions in the world. The postdoctoral fellows emerging from our rich academic environment are imbued with the ultimate goal to seek long term success in academia, industry, government, or non-profit sectors. There is clear continued need for this program since cardiovascular disease remains the leading cause of death globally, according to the W.H.O., and is also among the top causes of mortality and morbidity in the U.S. This obligates our program, our institution, and the United States, to train investigators who will advance the forefront of cardiovascular biomedicine. No other training mechanisms exist at UCSD that provide support and training of postdoctoral trainees in the unique and specific cardiovascular disciplines of this grant. The Guiding Principles for the program are embedded in the rich history of this program and propelled us to maintain our original title of the grant - “Training in Cardiovascular Physiology and Pharmacology.” Yet, we highlight that this T32 program continuously evolves and seeks improvement. It provides broad exposure to the study of cardiovascular basic biology, physiology, disease pathobiology, and related translational pursuits. Primary areas that the program focuses on are 1) cardiac signaling, 2) cardiac development, regeneration, and stem cell biology, 3) cardiac genetics and epigenetics, 4) cardiac bioengineering, and 5) cardiac clinical and translational focused biology. Within these areas of focus we foster exposure of the trainees to the most modern, innovative, and emerging technologies to accelerate their hypothesis driven discoveries. This might include use of human stem cell-based model systems, omics-based approaches, computational sciences, and big data informatics, and how best to translate from bench to the bedside. During the success of this T32 program over the last forty years of continuous support, it has been instrumental in training many of the leaders in cardiovascular biology at UCSD, and also has had broad impact on producing leaders throughout the country in both academia and industry.

NIH Research Projects · FY 2026 · 1979-07

PROJECT SUMMARY The urgency and importance of training critically needed basic, translational, and clinical scientists in women's health and reproductive research is well recognized by the leadership of NIH, the national government, and the scientific and medical communities. The UCSD Training Program in Reproductive Sciences takes a distinctive multidisciplinary approach to training postdoctoral scholars as physician-scientists and reproductive biologists in the mechanistic investigation of reproductive processes and diseases. The combination of clinical, physiological, coputational, and molecular approaches to studying reproductive processes and disorders creates exceptional training for basic scientists and physician-scientists, producing well-rounded reproductive researchers who are extraordinarily qualified for future careers. The program supports both fellows seeking advanced research experience post-Ph.D. and/or M.D., including those seeking research and clinical training to become board- certified OB/GYN subspecialists. Thus, the leadership and mentor team are well balanced between clinical and basic researchers. We have an exceptional 40-year track record as recognized by an NIH Mentor Award (10 yrs 2003-2012) and a perfect score of 10 awarded by the study section for the 2013-2018 application. Review panels have approved 4 positions for many years, however, NICHD has funded only 3. We primarily support trainees for their first research year, after which they seek F32 or K awards. A cohesive group of NIH-funded faculty from the Department of Obstetrics, Gynecology and Reproductive Sciences and the Departments of Medicine and Pathology at UCSD with common interests, shared grants, and joint publications, provides basic, translational, and clinical training, and fosters the careers of the trainees. The majority of the faculty are members of the UCSD Center for Reproductive Science and Medicine, the Center for Perinatal Discovery, and/or mentors in the UCSD Women's Reproductive Health Research Program. Thus, this training program is integrated with multiple centers, allowing the faculty and fellows to interact at many levels, creating an atmosphere of collaboration, mentoring, and career support. Our research ranges from computational and molecular to patient-oriented research utilizing bioinformatics, in vitro analyses, cell culture models, whole animal, and clinical research methodology. The breadth of the research opportunites for our trainees covers the lifspan: germ cells, placental growth and function, gonadal physiology and development, pituitary/hypothalamic development and neurophysiology, puberty, pelvic floor muscle biology, vaginal, urinary, and gut microbiome, metabolism and stress, and epidemiology of infertility and preterm birth. The program of training includes group meetings and presentations, journal clubs, seminars, national meetings, clinical and lab training, independent research, career development workshops, grant writing, Independent Development Plans, and coursework in biostatistics, rigor and reproducibility, ethics, and an innovative “Thesis Committee” team mentoring structure. Our aim is to continue to prepare exceptional physician-scientists and basic scientists to become the future leaders in academic reproductive research.

NIH Research Projects · FY 2025 · 1978-12

PROJECT SUMMARY Gross chromosomal rearrangements (GCRs) are mutations that underlie many genetic diseases. Many cancers have increased accumulation of GCRs, which likely represents a type of mutator phenotype thought to be important for the development and progression of these cancers. Consistent with this, some inherited cancer susceptibility syndromes result from genetic defects that cause increased accumulation of GCRs in model systems. While many pathways thought to play a role in preventing GCRs have been studied, a comprehensive understanding of the genes, pathways and mechanisms that prevent accumulation of GCRs is not available. Understanding these mechanisms will impact on human health for several reasons: 1) Identifying genes and mechanisms that suppress and promote GCRs will provide tools to identify causes of genome instability in cancer; 2) The development of PARP inhibitors for treating cancers with BRCA1 and BRCA2 defects has demonstrated that defects causing genome instability are potential therapeutic targets for cancer; and, 3) Understanding pathways that suppress accumulation of GCRs, including identifying synthetic lethal partner genes for these pathways, will provide critical information for guiding developing of novel cancer diagnostics and therapeutic approaches for use in personalized approaches to cancer treatment. The goal of this proposal is to use Saccharomyces cerevisiae to identify genes, pathways and mechanisms that suppress GCRs that will then guide the development of assays for the formation of GCRs in human cells. Key related objectives are to identify chromosomal features and aberrant DNA repair mechanisms that contribute to the formation of GCRs and to identify human genes in which defects cause genome instability in cancer. The proposed studies will build on the results of work supported by this project that have resulted in a series of quantitative assays for use in studying GCRs and have identified numerous genome instability suppressing (GIS) genes and cooperating GIS genes that suppress the accumulation of GCRs in S. cerevisiae. The following lines of research will be carried out: 1) The mechanistic features of selected pathways that suppress GCRs will be investigated, focusing on Tor2 (a tumor suppressor homologue), the cohesion and condensin complexes, and Exonuclease 1; 2) Genetic studies and whole genome sequencing will be used to identify the genes and mechanisms that suppress or promote GCRs mediated by the formation of large loop ssDNA hairpin-mediated GCRs and study the genomic features that underlie the formation of specific GCRs; 3) The mechanistic and genetic features of the formation of individual GCRs will be studied using a newly developed assay that allows monitoring of the formation of an individual GCR by PCR; and, 4) GCR assays for use in human cells will be developed and used to investigate defects in human GIS genes. These studies will provide a comprehensive picture of the pathways and mechanisms that prevent GCRs in S. cerevisiae and provide insights into the origin of genome instability in cancer.

NIH Research Projects · FY 2026 · 1978-09

Summary The purpose of this Training Program is to train scientists in Experimental Endocrinology and Metabolism to be the future leaders of academia, who will generate the new ideas, and of the biopharmaceutical industry, who will translate these ideas into practical therapies. We strive to enable our Trainees to be capable of performing high quality biomedical research in clinical or basic areas of Endocrinology and Metabolism. We will provide Trainees a wide variety of opportunities in both traditional and novel areas of Endocrinology/Metabolism, including but not limited to: clinical studies of the pathophysiology and therapy of diabetes and obesity; basic studies in intermediary metabolism and diabetes, lipid and lipoprotein metabolism, immunological mechanisms in atherogenesis, the role of thyroid metabolism in cardiac metabolism; neuroendocrine control of reproduction; lipid-mediated cellular signaling pathways; and endocrine and nuclear receptors mediated regulation of cellular metabolism. The program is centered within the Division of Endocrinology and Metabolism of the Department of Medicine, but includes faculty with relevant interests in other basic and clinical departments of UCSD, as well as faculty from closely associated Institutions. The 20 Mentors selected to be Faculty include both established senior faculty who continue from previous cycles, as well as younger faculty who have stellar scientific credentials, but who will be the future leaders of our Training Program. The program will include: (1) intensive laboratory and/or clinical research training, (2) laboratory meeting, seminars and other conferences, (3) formal course instruction and (4) oversight by Mentors and the Executive Committee. The primary focus is the research undertaken by trainees under close supervision of their Mentor. The goal is for the trainee to increasingly assume an independent scientific role in their research. Weekly lab meetings provide opportunities for constructive critique, and frequent seminars provide opportunities for intellectual growth. Trainees participate in weekly Endocrine Grand Rounds and other Division activities as appropriate, such as Journal Clubs, where admixtures of basic and clinical science are discussed. This provides cross-exchanges that have proven to be highly stimulating and even led to productive research collaborations. Trainees take 3-4 quarters of formal course work, depending on background, including a required course entitled “Biomedical Research Ethics.” All Postdoctoral Trainees at UCSD develop and complete a five-year “IDP” (Individual Development Plan), which is monitored by the Mentor and the Executive Committee of the Training Program, which will meet annually with each Trainee to both review the Trainee’s progress according to the IDP, as well as to provide advice and/or assistance to ensure that the Trainee’s overall career goals are met. Thus, this training program expands and brings together various activities encompassing the training and education of postdoctoral fellows in the fields of Endocrinology and Metabolism.

NIH Research Projects · FY 2025 · 1976-07

This application requests a renewal of support for the UCSD “Research in Infectious Disease” T32 Training Grant, with an updated scientific focus and leadership. The program, now in its 40th year, supports the career development of physician scientists who wish to pursue research training in infectious diseases (ID) and host- pathogen interactions. The goal of the T32 is to recruit trainees who wish to pursue rigorous research training that will place them on the pathway to productive, independent research careers. Because of the complexity of contemporary biomedical research and the highly competitive funding environment (especially for early career research scientists). The high level of commitment to each trainee in terms of training duration and intensity, coupled with the multidisciplinary character of the training experience has attracted outstanding applicants and has enabled them to be extremely successful in progressing to the next stages of development of careers as physician scientists. Based on a recently completed strategic planning process, we have devised a new leadership structure, recruited new world class research faculty, kept successful educational and training elements, while incorporating innovative new offerings -- all galvanized to address one of the greatest challenges facing modern medicine and public health: the global antibiotic resistance crisis. Our renewal proposal for Postdoctoral ID Training at UCSD, which we retitle “CARING: Combating Antibiotic Resistance into the Next Generation” leverages the institutional investment and educational resources of a major campus- wide initiative – the Collaborative to Halt Antibiotic-Resistant Microbes (CHARM). We retain core elements of our training structure that have yielded excellent trainee outcomes, including recruitment and selection processes that enlisted trainee cohorts with significant diversity from URM groups, unique T32 Fellow educational curricula (e.g. the CREST program) and our Mentors-in-Development (MiD) program for junior faculty. The fundamental change to our program is the AMR focus of research training, organized in 6 themes: 1) Deciphering Microbial Virulence; (2) Host Defense & Vaccinology, (3) Novel Therapeutic Discovery, (4) Microbiome Science, (5) Systems Biology & Engineering, and (6) Clinical Microbiology & Therapeutics. We have selected a world-class faculty the top 29 leading investigators with proven mentorship skills to comprise our new Research Training faculty (12 continuing + 17 new). Instead of 6 MD fellow slots, we will recruit talented Adult and Pediatric ID fellows across 5 MD slots + 2 PhD postdoctoral scientist slots to encourage interdisciplinary synergies between clinical and basic scientists. Dr. Victor Nizet, an eminent UCSD ID Physician-Scientist (>450 papers) with a superlative track record in postdoctoral fellow mentorship (>20 former trainees now independent faculty running research programs) assumes the role of Program Director. The overarching goal of the training program remains to prepare the next generation of ID physician scientists for highly productive careers in biomedical research with local, national and international impacts.

Other NSERC · FY 2024

Metal-Organic Frameworks, Inorganic Synthesis, Organometallic Chemistry, Organic Synthesis, Heterogeneous Catalysis, Hydroformylation, Group 9 Transition Metals, Main Group Chemistry

Other NSERC · FY 2024

human-computer interaction (HCI), computer-supported cooperative work, computer-mediated communication, educational technology, learning sciences, interface design

Other NSERC · FY 2024

cell biology, molecular biology