Stanford University

NIH Research Projects · FY 2025 · 1987-09

The global burden of disease caused by microbial pathogens is one of the largest challenges facing the biomedical community. Threats of emerging infectious disease and resistance to antimicrobial therapies highlight the growing need for vaccines and therapeutics, plus training programs for scientists to ensure ongoing cuttingedge research will improve human health. The rationale for this Training Program, active for 35 years, is the necessity for increased knowledge of the complex interactions between pathogens, microbiota, and the host immune system. The multi-disciplinary Microbiology & Immunology department is a rich environment where students learn to challenge established thinking and address scientific challenges. We aim to train the best and brightest students and postdocs, with mentoring in the laboratories of Program faculty to gain the skills needed to develop rigorous, impactful, well-funded research programs at the leading-edge of research in host-microbial interactions. We provide a strong foundation in fundamental research elucidating the molecular mechanisms of microbial pathogenesis and host-microbe interactions, while emphasizing translational research, human studies, and the problems that clinicians face in the treatment of infectious disease. Additional key elements of the training program include rigorous coursework, trainee-invited speakers, a departmental scientific conference for presentation and interaction, and a student-organized scientific retreat for cohesion and scientific exchange. Trainees are involved in teaching activities and are provided opportunities to become effective mentors and teachers, including a required TA-ship. Program enhancements include added learning in critical concepts in responsible conduct of research and increased emphasis on gaining knowledge in performing rigorous and reproducible research through formal courses taught by Program faculty, and laboratory training. Graduate student trainees are appointed upon admission to Stanford for up to 2 years; postdocs typically for 1 year; we are requesting renewal of 6 graduate and 2 postdoctoral slots per year for 5 additional years of funding. Required trainees-advisor IDP meetings along with substantial events and resources in career development facilitate transitions into the biomedical workforce; for the past 10 years we have exceeded our goal of 95% retention of our trainees in STEM-related fields. The Program benefits from the exceptional environment and we leverage substantial School of Medicine and University resources, programs, and engagement. Students and postdocs are successful, publishing high-impact papers and finding leading positions in all aspects of science, from research to teaching to consulting to policy. Over our history, we have trained many who are now leaders in biomedical research and we hope to continue this important and highly successful Training Program

NIH Research Projects · FY 2025 · 1985-09

Project Summary / Abstract We are seeking renewal of our long-standing training program in Cellular and Molecular Immunobiology to continue providing cutting-edge predoctoral training that leads to a PhD in Immunology. Considering the latest NIAID guidelines on training grant slot caps, combined with the ever-growing demand for access to our predoctoral training program, we are requesting support for 8 predoctoral trainees in this renewal. Our program offers comprehensive research training in the labs of Stanford immunologists, whose work spans basic, computational, translational, and clinical immunology. A key focus of the program is systems analysis within human immunology, equipping students to explore complex biological networks and apply integrative approaches to understanding immune responses in health and disease. The curriculum emphasizes critical thinking and the analysis of current immunological challenges, supplemented by seminars from leading immunologists nationwide. Additional pillars include teaching opportunities, training in the responsible conduct of research, and development of strong written and oral communication skills. Our predoctoral trainees are drawn from a highly competitive and diverse applicant pool, recognized for their academic and research excellence. The program prioritizes individualized advising and mentorship, with a flexible curriculum tailored to meet the unique goals of each student. Students benefit from a stimulating, supportive training environment and may choose between two curriculum tracks: the traditional Molecular, Cellular, and Translational Immunology (MCTI) track, or the Computational and Systems Immunology (CSI) track, which integrates computational and systems methodologies to enhance the understanding of immune processes at the systems level. This interdisciplinary program unites a distinguished faculty from 21 departments across Stanford’s medical school and university, supported by world-class resources and facilities. The success of the program is demonstrated by the strong publication record of our trainees, their contributions to advancing immunological research, and their leadership in diverse scientific careers.

NIH Research Projects · FY 2025 · 1984-07

For over four decades, the Stanford Biomedical Informatics (BMI) Training Program has granted PhD and MS degrees to graduates who have made significant contributions to biomedicine and health through data-driven and computationally-derived scientific discoveries and advances. Today, our trainees have access to unprecedented amounts of biomedical data that span our entire biomedical enterprise, and they are empowered by their training in biomedical informatics and data science to advance the biomedical life sciences and improve clinical care. Our proposal for the future of BMI training at Stanford harnesses the opportunity to produce the next generation of researchers who will enable precision medicine through innovations in translational bioinformatics, health care informatics and clinical research informatics. We receive annual support for training 11 pre-doctoral candidates (including two candidates in HIV informatics) and 4 postdoctoral candidates for a period of 5 years. Our trainees benefit from a rich curriculum that consists of specially designed core courses in biomedical informatics and data science, technical electives from companion fields of computer science, statistics, mathematics and engineering, domain electives in biological and clinical sciences, and instruction on the principles of responsible conduct of research and the methods of rigor and reproducible research. Our trainees are provided with outstanding mentored research opportunities offered by 34 investigators who collectively represent 16 departments and divisions across 3 schools at Stanford University. Beginning August 2021, the BMI training program benefited from the establishment of the Department of Biomedical Data Science (DBDS) at Stanford, for which it is now the primary graduate training program. DBDS serves as a critical nexus to increase the education and research opportunities for our BMI trainees. Our environment is well-positioned for such expanded opportunities due to a recent explosion of highly successful initiatives including the Institute for Human-Centered AI (HAI), the Center in Artificial Intelligence in Medicine Imaging (AIMI), and the Center in Digital Health (CDH). In addition, our training covers issues related to responsible AI and data science in research –including rigor, reproducibility, privacy and security. Through these efforts and others, Stanford University remains a fertile environment to advance human health through training in biomedical informatics and data science.

NIH Research Projects · FY 2025 · 1982-01

Mechanistic intermediates in copper oxygenases and oxidases: Copper oxygenases and oxidases have a wide range of functions including melanin and siderophore biosynthesis, neurotransmitter regulation, iron metabolism, and proton pumping for ATP synthesis. Understanding their reaction mechanisms is both of fundamental importance and has significant downstream applications in health, biotechnology, and catalysis. There has been much mechanistic speculation based on structures, model complexes, and calculations. However, the key to determine the enzyme mechanisms and thus utilize and control their reactions is by trapping catalytic intermediates and defining their structures and reactivities. Our research combines enzyme kinetics to trap intermediates, a range of spectroscopies to define these intermediates, and electronic structure calculations correlated to experiments to elucidate reaction mechanisms. Our focus is on the three classes of copper oxygenases and oxidases. The antiferromagnetically “coupled” binuclear Cu enzymes include catechol oxidases (CaOx), tyrosinases (Ty), and o-aminophenol oxidases (AOx) that all utilize the same µ-η2-η2 CuII2O22− intermediate to perform their functions. In Progress, trapping the ternary intermediate of OxyTy with phenol substrate bound has defined the Ty monooxygenase mechanism, and our studies are now directed toward determining the mechanisms of the CatOx’s and the AOx’s and how these enzymes are tuned for their selectivity. The “non-coupled” binuclear Cu enzymes include dopamine β-monooxygenase that converts dopamine to norepinephrine, the insect homolog tyramine β- monooxygenase, and peptidylglycine ⍺-hydroxylating monooxygenase. In this class, the two Cu’s are separated by 11Å resulting in the lack of magnetic coupling. A major point to address is whether co-substrate binding induces a conformational change to bring the Cu’s together for coupled binuclear O2 activation or if the 11Å structure is active. If the latter, important issues will be explored including whether O2 activation by a single Cu (a CuII–O2− intermediate) is able to perform H-atom abstraction and the timing of electron transfer from the 11Å Cu required to complete the reaction and avoid reactive oxygen species (ROS). The third class is the multicopper (MCOs) and heme–copper oxidases (HCOs) that reduce O2 to H2O, using different active site structures for different functions. The MCOs use a trinuclear Cu cluster for efficient oxidation of substrates, while the HCOs use their binuclear site to pump protons across a membrane for ATP synthesis. Studies on the MCOs are far along in defining their mechanism of O2 reduction, their role in Fe metabolism with control of ROS, and coupling to electrodes for fuel cell applications. For the HCOs, intermediates are available that would elucidate the O–O bond cleavage mechanism and the active site structural changes that enable proton pumping. However, the dominant spectral features of the hemes have precluded defining the role of the Cu and its Tyr-crosslinked His ligand in these reaction steps. New spectroscopic methods being developed will enable definition of the complete Heme/Cu/Tyr active site and its role in the O–O cleavage and proton pumping mechanisms.

NIH Research Projects · FY 2026 · 1981-07

This competing renewal of the Postgraduate Training Program in Epithelial Biology, AR07422, aims to extend 40 continuous years of NIH-supported postdoctoral training in skin research at Stanford. The program objective is to train postdoctoral fellows for future careers in research relevant to skin diseases. The rationale for the multi-disciplinary design of the program within the Stanford Program in Epithelial Biology is based on the premise that future success in cutaneous biology research will be enhanced by training interactions within a broad scientific network. Developments during the prior funding cycle include: 1) Expansion of the Stanford Program in Epithelial Biology (PEB): AR07422 is the heart of the multi- disciplinary PEB, which has grown to 74 Stanford faculty united by themes common to skin and other epithelial tissues, including differentiation, morphogenesis, adhesion, stem cell biology, carcinogenesis, and therapeutics, which together comprise T32 training foci. The current proposal has also expanded to include training opportunities in translational and population sciences research, directed by world leaders in those fields. 2) Enrichment of the T32 training environment: Embedded among basic science faculty, the core Dermatology labs leading this T32 have been further enriched by 24 Ph.D. students pursuing thesis efforts, a 25% expansion in research space in 2016, new equipment, new high throughput genomics core facilities, and a new in-lab core biocomputational training resource. 3) Enhancement of multi-disciplinary resources available to trainees: In addition to the PEB, T32 mentors expanded their involvement and leadership in additional multi-disciplinary programs at Stanford, spanning Stanford Stem Cell Biology, Cancer Biology, Biomedical Data Sciences, and Genomics Programs. 4) Acceleration of the scientific productivity of the Stanford skin research training community: Productivity, measured by high impact papers (journal ISI impact factor >25) has accelerated, with 21 such publications from the core Dermatology mentors over the prior funding cycle. 5) Successful training of future PIs: 11 Research P.I.s graduated from the laboratories of the 4 Dermatology core mentors over the current funding cycle and are now Assistant Professors at institutions that include Baylor College of Medicine (1); Icahn School of Medicine at Mount Sinai (1); University of Southern California (USC)(1); Yale School of Medicine(1); University of California San Francisco (UCSF) (1); Lausanne University Hospital, Switzerland (CHUV) (1), Shanghai Jiao Tong University School of Medicine (1); Shenzhen Institute of Advanced Technology, China(1); Sun Yat-Sen University, China (1); Ulsan National Institute of Science and Technology, South Korea (1); Uppsala University, Sweden(1).

NIH Research Projects · FY 2026 · 1981-07

Project Summary/Abstract: This renewal involves integrated and interdependent synthetic, mechanistic, structural, biochemical mode of action, computer modeling, collaborative and preclinical studies directed at the design, synthesis, assay and advancement of fundamentally new and unique therapeutic leads and strategies directed at unsolved global human health problems: the eradication of HIV/AIDS, novel treatments for Alzheimer's disease and multiple sclerosis, and the use of small molecules to enhance antigen density in antigen-targeted CAR T/NK cell therapies and cancer immunotherapy. HIV is one of the most catastrophic pandemics to confront mankind. Current antiretroviral therapy (ART) addresses the active virus, allowing one to live with HIV/AIDS, but with cost, compliance, resistance and chronic chemoexposure challenges. ART is not curative. Reservoir cells incorporating genomically encoded provirus episodically resupply the active virus. Elimination of these reservoir cells if done with ART is thus one of the most promising strategies to eradicate HIV/AIDS. Modulation of protein kinase C (PKC) represents one of the best strategies to activate reservoir cells for subsequent clearance by the immune system, antibodies or immunotoxins. PKC modulators are also leading candidates for treating Alzheimer's disease (in current clinical trial), for cancer immunotherapy (clinical trial proposed for 2021), for multiple sclerosis and for many other unmet therapeutic needs. The lead PKC modulator, bryostatin 1, has been entered into clinical trials for AIDS eradication and Alzheimer's disease and is expected to be used clinically in a CRADA conducted by NCI scientists to enhance antigen expression in antigen targeted CAR T cell therapies for children with acute lymphoblastic leukemia who fail cell therapy because of low antigen density. Enabled by our scalable (now GMP) synthesis of bryostatin which represents the sole major supply of clinical grade material and our computational and REDOR solid state NMR structural studies relevant to bryostatin binding to PKC, plans are presented for the design, synthesis and evaluation of uniquely accessible “close-in” bryostatin analogs, super simplified analogs and two new families of clinically relevant PKC modulators, collectively directed at the identification of more efficacious, better tolerated and more synthetically accessible clinical candidates. New candidates will be evaluated in a range of “in house” assays and in advanced assays conducted by a network of collaborators expert in the clinically targeted areas.

NIH Research Projects · FY 2025 · 1977-09

This application requests funds to continue the highly successful Cancer Biology T32 training program at the Stanford University School of Medicine. The current application will present a new vision for this training program, in which the innovative technologies developed and used at Stanford will become a cornerstone of the cancer research program, in a proposal entitled “Leveraging innovative technologies in basic and clinical cancer research”. The goal of this training program is to provide the very best training for its predoctoral trainees so that they become successful and independent leaders in the field of cancer research. The program accomplishes this goal by providing each trainee with a broad and comprehensive curriculum, a vast array of educational resources such as seminars, lectures, conferences and workshops specifically geared toward the biology of cancer, a faculty comprising 49 exceptional preceptors with extensive experience in cancer research mentoring, and an unparalleled research environment. The success of the training program is demonstrated by its track record of attracting outstanding and talented predoctoral candidates to Stanford University and placing graduates of the program in high-profile competitive cancer research positions in academia, industry, and medicine. During the next 5-year period, there will be a number of new initiatives. The program will focus on leveraging a variety of cutting-edge technologies pioneered by T32 faculty at Stanford to better understand cancer development and to help develop improved cancer diagnostics and therapeutics. The strong technology emphasis of the program is a key strength that will promote a truly multidisciplinary approach to cancer research, enabling collaborations between individuals in varied fields such as systems biology, functional genomics, epigenetics, immuno-oncology, and cancer stem cell biology. In addition, the research conducted by T32 preceptors has a significant clinical focus, with the goal of ultimately improving cancer care. Our curriculum, which we have designed to provide trainees with a solid core of cancer biology coursework while allowing flexibility in electives to match individual needs in areas of specialization (e.g., computational biology), will now also include technology-oriented coursework. We have also introduced a clinical course to expose students to the translational side of cancer biology as well as “T32 chats” to teach students about translational cancer biology and pitfalls associated with various technologies. We are promoting career development by providing leadership opportunities for students, access to teaching opportunities, and career workshops with alumni to give exposure to different potential career options. To ensure optimal mentors, we will also have a new rigorous selection process for T32 preceptors. To ensure the most robust training program possible, we consult with internal and external advisory committees comprising highly accomplished scientists at Stanford and peer institutions. These collective experiences will provide T32 trainees with a strong foundation in cancer biology to prepare them for independent careers and for becoming the next generation of leaders in this field.

NIH Research Projects · FY 2025 · 1976-07

Project Summary The T32 Training Program in Diabetes, Endocrinology and Metabolism at Stanford University (Endocrine T32) serves a national need to train physician and basic scientists in the fields of diabetes, endocrinology and metabolism. The Endocrine T32 has a remarkable 46-year record of rigorous scientific training; producing numerous current and emerging endocrine research leaders. The goal of this renewal is steadfast pursuit of this critical purpose. The Endocrine T32, the only postdoctoral research training program in diabetes, endocrinology and metabolism at Stanford, is integrated into an extraordinary research environment, including the Stanford Diabetes Research Center, and unparalleled training activities, seminars and resources. The training program will provide M.D. and Ph.D. postdoctoral trainees (four per year, evenly split), a uniquely rich and supportive environment to learn innovative research approaches. Supported by the Endocrine T32 for two years, trainees will pursue cutting-edge research in the laboratories of remarkably accomplished investigators and experienced mentors. The training faculty include 28 investigators from nine basic science and clinical Departments, whose interests converge on four themes (Islet and Beta-cell Biology; Obesity, Metabolism and Diabetes Complications; Interventional and Population Diabetes; Endocrinology and Population Health Sciences); integrating a wide spectrum of diabetes- and endocrinology-focused laboratory, clinical, translational, epidemiologic and health disparities research. Mentors will participate in formal training workshops to ensure supportive and inclusive training. Trainees will receive a structured curriculum of study that includes weekly seminars, an Endocrine T32 specific series (where they present and critique the work of others) and career-pertinent didactic courses, including the Responsible Conduct of Research, biostatistics and computation/computer programming. These efforts foster a stimulating, cohesive and productive training experience that engenders the knowledge and skills necessary to emerge research leaders. To safeguard trainee success, they will formulate a Career Development Committee that assesses research progress, encourages professional development and co-navigates the trepid transition to independence. Over the past 15 years, 85% of our trainees have remained in science; to continue this success, trainees will develop and submit Career Award applications through participation in grant-writing bootcamp. In recognition of the challenging, long gestation of (physician) scientists, robust (>$300,000 per year) institutional support that augments trainee salary and bridge funding will be provided. The Program will take concrete steps to address a historic lack of inclusivity, including Internal and External Advisory Committees with expertise in the recruitment and retention of underrepresented individuals and that ensure programmatic accountability. The goal of this Training Grant is to educate a diverse cadre of promising postdoctoral (physician) scientists that become the future leaders of academic, governmental and industrial in endocrine research.

NIH Research Projects · FY 2025 · 1975-07

This T32 application seeks to extend funding to a thriving research training program in the NIDDK mission areas of adult and pediatric Gastroenterology and Hepatology at the Stanford University. The main goal of the Program is to recruit the most talented young physician-scientists in basic, translational, clinical and population-based research and train them to be future leaders in academic gastroenterology. The Training Program has a well-functioning governing structure consisting of a highly motivated Program Director with a very strong track record of research training and NIH funding, and Oversight, Selection, Mentorship and Evaluation Committees. Additional support is obtained from an Administrative Subcommittee and an Internal and External Advisory Committees. The Program includes faculty in the adult and pediatric GI Divisions and exceptional scientists at Stanford who have strong track record of mentoring trainees in GI. The mentors cover a wide range of expertise providing a comprehensive and interactive training including (1) basic biology of enteric and hepatic pathogens and the development of novel therapeutic strategies; (2) host-microbiome interactions; (3) mucosal immunology; (4) liver pathophysiology; (5) cancer genomics and biology; (6) bioengineering and medical device development; (7) population science and epidemiology; and (8) health services and clinical outcomes research. For trainees in the latter categories, Master’s degree program in epidemiology, health policy/services research or biomedical informatics is offered. The Training Program is structured to optimize its operations in (1) selecting the best candidates, (2) facilitating mentors to create the most productive research training experience, (3) monitoring trainees’ progress and providing necessary support, and feedback, and (4) critically evaluating the Program for continuous improvement. The Program is enriched by Stanford’s strong academic environment and commitment to train physician- scientist leaders of the future. Our Program has excelled and majority of our graduates from the last cycle are pursuing an investigative career in academic institutions. We propose to continue the strong tradition of physician-scientist training, adherence to all ACGME recommended practices and seek to enhance it to best prepare our trainees for the future of digestive medicine.

Other NSERC · FY 2024

Learning from Demonstration, Human-Machine Systems, Human-Robot Interaction, Surgical Robotics

Other NSERC · FY 2024

Land Plants, Nutrient Cycling, Oxygen Cycling, Land Plant Evolution, Geochemistry, Palynology, Paleobotany, High Arctic, Redox balance

Other NSERC · FY 2024

natural language processing, text generation, machine learning, neural networks, semantics, natural language understanding, commonsense reasoning, multimodal machine learning, word embeddings, data augmentation

Other NSERC · FY 2024

Protein biophysics, Computational modelling, Structural biology, Machine learning, Biomedical engineering, Chemical physics, Systems biology, Molecular networks, Drug discovery

Other NSERC · FY 2024

decentralized water technologies, water supply and treatment, decarbonization, water supply resiliency, techno-economic analysis, spatial and temporal modeling, water quality, urban infrastructure, process engineering, urban water policy

Other NSERC · FY 2024

Ultrasound Imaging, Ultrasound Molecular Imaging, Targeted Microbubbles, Ultrafast Ultrasound Imaging, Neural Network, Kidney Cancer, Beamforming, Image Enhancement, Molecular and Cellular Imaging, Deep Learning

Other NSERC · FY 2024

Water Reuse, Anaerobic Wastewater Treatment, Chemistry, Potable Reuse, Non-potable Reuse, Energy Sustainability, Wastewater Treatment, Energy-Neutral, Environmental Engineering, Water Treatment

Other NSERC · FY 2024

Many-body perturbation, Low dimensionality, Optical excitations, Moiré potential, High-performance computing, Transition metal dichalcogenides, Parameter-Free ab initio calculation, Charge and energy dynamics, GW plus Bethe-Salpter-Equation, Quantum information science

Other NSERC · FY 2024

Geometric Analysis, Partial Differential Equations, Systolic Geometry, Riemannian Geometry, Curvature

Other NSERC · FY 2024

Total synthesis, Natural product, alkaloid, pyrroloiminoquinone, cycloaddition, thiocarbonyl ylide

Other NSERC · FY 2024

Epigenetics, Cellular Plasticity, High Throughput, Chromatin Accessibility, Therapeutic Resistance, Breast Cancer, Automation, Cell State Transition

Other NSERC · FY 2024

Bioelectronics, genetic targeting, step growth polymerization, conductive polymer, Paal-Knorr reaction, channel opsin, polypyrrole

Other NSERC · FY 2024

combustion, low-carbon fuels, hydrogen-rich fuels, reaction rate, shock tube, chemical kinetics, fuel blends, ammonia, hydrogen, laser diagnostics

Other NSERC · FY 2024

Magnetic Resonance Imaging, Electromagnetic Design, Mechanical Design, Medical Imaging, Molecular Imaging, Contrast Enhanced, Delta Relaxation Enhanced, Boundary Element Method, Finite Element Method, Nuclear Magnetic Resonance

Other NSERC · FY 2024

Turbulence, Boundary layers, Hypersonic flow, Wall modelling

Other NSERC · FY 2024

Polymer chemistry, Organic electronics, Dynamic interactions, Self-healing, Chemical recycling, Organic synthesis, Bioelectronics, Supramolecular chemistry, Semiconducting polymers, Degradable polymers