Weill Medical Coll Of Cornell Univ

NIH Research Projects · FY 2026 · 2007-01

PROJECT SUMMARY The Weill Cornell Medicine - Rutgers New Jersey Medical School Clinical Trials Unit (WCM-NJMS CTU) will conduct National Institute of Allergy and Infectious Diseases (NIAID)-sponsored network studies of HIV treatment and HIV prevention; enroll participants from the different communities of the New York City (NYC)-Newark metropolitan area, the epicenter of the HIV epidemic in the U.S. -- home to 14% of Americans living with HIV; and contribute to the networks' scientific agendas. The unit consists of a central core facility and three clinical research sites (CRS). The WCM-NJMS CTU provides central research support to the three CRSs, including investigative and laboratory oversight, financial administration, quality assurance, training, and community engagement. The three CRSs, WCM-Uptown, WCM-Chelsea, and Rutgers NJMS, are located in different parts of the NYC-Newark metropolitan area and serve the different populations of people living with or at-risk for HIV. The WCM-Uptown CRS is located close to Harlem, with some neighborhoods demonstrating HIV seroprevalence rates of over 5%. The WCM-Chelsea CRS is located in Chelsea, with some neighborhoods demonstrating the highest seroprevalence rate in NYC of over 8%. The Rutgers NJMS CRS is located in the center of Newark, serving a predominately African American population with a high proportion of women, with some neighborhoods demonstrating an HIV seroprevalence rate of over 5%. WCM-NJMS CTU investigators are leaders in the field who are shaping the HIV treatment and HIV prevention research agendas. They are highly experienced with expertise in HIV cure strategies, antiretroviral drugs and treatment strategies, tuberculosis, and HIV comorbidities, including hepatitis and neurologic complications as well as HIV prevention strategies, including HIV pre-exposure prophylaxis (PrEP) and integrated strategies. Community engagement is a key strength of the WCM-NJMS CTU with both site-specific and joint Community Advisory Boards (CABs) and a strong record of effectively communicating study results back to the community. The CTU's three CRSs have successfully enrolled over 1000 participants into a wide variety of HIV treatment and prevention trials during the current grant cycle with outstanding retention and data quality. Furthermore, CTU investigators have made substantive scientific and leadership contributions to the networks. In summary, the WCM-NJMS CTU brings together a broadly experienced group of recognized investigator leaders who will work with an experienced clinical research staff to conduct cutting-edge HIV treatment and HIV prevention studies in the NYC-Newark metropolitan areas.

NIH Research Projects · FY 2026 · 2006-09

We propose a summer clinical immersion program at the Weill Medical College of Cornell University that brings 20 Engineering PhD students per year interested in biomedical applications from Ithaca Engineering College Campus to New York City Medical College Campus for short-term dedicated intensive clinical exposure in the summer between their first and second year of graduate training. Each student will take bioethics lectures, shadow clinical practitioners and participate in clinical related research under the direction of a clinician mentor. This clinical summer immersion is designed to connect BME to healthcare and society and to steer and enhance students’ research interests towards medicine. It will immediately impact their PhD thesis research by adding a medical conscience and influence their long term career towards improving healthcare.

NIH Research Projects · FY 2025 · 2003-09

Over the past 5 years, Cornell’s Roybal Center–The Translational Research Institute on Pain in Later Life (TRIPLL) has developed innovative approaches and an effective infrastructure for the translation of behavioral and social science research to improve the health and well-being of older adults. A major strength of TRIPLL is its demonstrated ability to link behavioral and social science research to real-world contexts. TRIPLL has supported the development of behavioral intervention trials that leverage new technologies to bring about adaptive behavior change in the context of pain, an issue characterized by the Institute of Medicine as a critically important and under-addressed public health problem. In this renewal application, we propose to build on our accomplishments to date by measurably expanding the infrastructure of the Center to augment the development of scalable behavioral interventions for pain mitigation. We will maintain program elements that have helped TRIPLL achieve success (e.g., frequent oversight of supported projects) and add new elements (e.g., an Industry Advisory Board to promote collaborations with industry partners and advise on commercializing Center products) to attain additional successes. We will also build on our capacity to test potent and scalable behavioral interventions for pain, targeting specific Mechanisms of Behavior Change (MoBC), and help to advance interventions along the NIH Stage Model continuum with particular emphasis on later stages. The expanded multidisciplinary collaboration among prominent research centers in Ithaca and New York City (NYC), including New York City-based Weill Cornell and Cornell Tech, constitutes a major strength of this renewal application. TRIPLL’s overarching goal is to foster a culture of innovation and achievement that generates new knowledge in behavioral intervention development and effectively moves projects along the NIH Stage Model continuum. We will pursue the following specific aims: 1) Maintain a responsive leadership and administrative infrastructure to support intervention development for later-life pain across the NIH Stage Model, 2) Support and monitor innovative clinical trials that are anchored in the Mechanisms of Behavior Change MoBC and strive to ensure applicability in various groups of older adults; and finally 3) Leverage the intellectual, fiscal, and other resources of the academic and industry collaborators in this application and foster new collaborations with other NIA-funded Centers to achieve synergistic results that would not be attainable by any one institution. The proposed structure of the Center, its clinical trial development program, the support from multiple advisory committees, and the extensive array of resources will help TRIPLL measurably advance the science of behavioral intervention development to address a significant public-health problem: later-life pain.

NIH Research Projects · FY 2025 · 1999-07

The objective of this program is to train physician-scientists in basic, translational, and clinical biomedical research focusing on infectious diseases. The training program will use the resources of 3 allied institutions, co-located on the east side of Manhattan in New York City: Weill Cornell Medicine will be the primary institution with collaborators at Rockefeller University and Sloan-Kettering Cancer Institute. The program’s faculty are well-funded scientists with independent research support who are committed to research and training. They are complemented by 3 international collaborators from Brazil and Haiti. The faculty share the view that the physician-scientist truly is an endangered species and are committed to address this issue by establishing long-term mentoring relationships with postdoctoral trainees. The broad areas of research training are: immunology, malaria, mycobacteriology, virology, and translational/clinical research, including bacterial and fungal infectious diseases of global importance, and HIV/AIDS. Trainees and mentors will develop an individual development plan (IDP) that can include, for example, additional formal courses in the Weill Cornell Graduate School (e.g. immunology, molecular biology) or enrollment in a K30 Master’s in Clinical Investigation program. During the funding period (1999-2024), 58 trainees were appointed and 53 (100%) completed their training (5 continue in the program). Twenty-seven (51%) of 53 who completed the program received NIH K Awards and two are reapplying. Research subject areas included: drug-resistant bacteria, HCV, HIV, KSV-HHV8, malaria, schistosomiasis, and tuberculosis. A total of 70% hold current appointments at academic institutions and 79% currently conduct research. In total, 26 (49%) of T32 trainees completing the program were women, 10 (19%) were racial/ethnic minorities, and 2 were from disadvantaged backgrounds. The program will continue to recruit physicians who have completed their clinical training (medicine, pediatrics, pathology) and are seeking academic investigative careers as physician- scientists. This training grant will provide developing physician-scientists with the opportunity to make the transition from clinical training to research. We request to maintain 5 training slots a year for a training period of 2-3 years.

NIH Research Projects · FY 2026 · 1998-07

Alzheimer’s disease and related dementias (AD/ADRD) are leading causes of age-related cognitive impairment, currently untreatable. Increasing evidence indicates that functional alterations of the cerebral microcirculation may play a role in the pathogenesis of AD/ADRD by reducing the cerebral blood supply. The health of the brain requires a continuous supply of O2 and nutrients through blood flow, tightly matched to its dynamic and regionally diverse energy needs. Accordingly, neural activity increases blood flow in active brain regions (functional hyperemia). Functional hyperemia depends in large part on the link between NMDA receptor activity and neuronal production of the potent vasodilator nitric oxide (NO), and requires tissue plasminogen activator (tPA) for its full expression. The microtubule associated protein tau is a key pathogenic factor in AD and other ADRD caused by tau mutations (tauopathies), but little is known about its role in the neurovascular dysfunction associated in with AD/ADRD. Studies during the previous funding period have discovered that tau disrupts the link between NMDA receptor activity and NO production and suppresses functional hyperemia. Since, in tauopathies, including AD, neocortical neural networks are hyperactive, the failure of functional hyperemia could be particularly damaging by reducing the brain’s O2 supply in the face of the increased energy demands caused by aberrant network activity. In this renewal application we seek to address this critical issue by elucidating the neural and microvascular bases of the effects of p-tau on neurovascular coupling and on neural network activity, and their impact on brain O2 delivery. To this end, we will test the hypothesis that the neuronal NO deficit induced by p-tau disrupts the microvascular bases of functional hyperemia and leads to neural network hyperactivity, which, in turn, results in a potentially harmful reduction in brain O2. To this end, we will use advanced imaging approaches in awake PS19 mice, a tauopathy model, to test the following hypotheses: (a) The NO deficit induced by p-tau leads to aberrant neural network activity and disrupts the orderly microvascular events underlying functional hyperemia; (b) The combination of aberrant neural network activity and impaired functional hyperemia leads to reduced brain O2 availability, rescuable by O2 supplementation; (c) Restoring neuronal NO production with tPA counteracts neurovascular dysfunction, network hyperactivity, and reduced brain O2, and ameliorates tau pathology and cognitive dysfunction. These studies will unveil a new aspect of p-tau pathobiology related to a deleterious mismatch between O2 supply and demands, and may provide the mechanistic bases for new therapies for AD and other tauopathies.

NIH Research Projects · FY 2026 · 1997-12

Abstract Mammalian brains are extremely sensitive to metabolic perturbation. If blood glucose drops by only a factor of ~2, immediate neurological symptoms emerge, including delirium and coma. We identified nerve terminals as a one of the likely loci of this vulnerability, as the vesicle recycling program crashes very quickly upon fuel withdrawal. We hypothesize that this metabolic sensitivity may lie at the heart of both neurodegenerative and neuropsychiatric diseases, as brain hypometabolism is a strong predictor of the onset of these diseases (albeit on different time scales). We seek to address many fundamental knowledge gaps we have concerning how local synaptic metabolism is regulated, including what molecular machineries for metabolism support synapse function and how different metabolic fuels can be used to support synapse function. We recently determined that one of the ten enzymes needed for glycolysis serves as a critical control point for glycolytic flux in nerve terminals. Enhancing the activity of his enzyme, PGK-1, only 2-fold is sufficient to provide dramatic protection against hypometabolic synaptic dysfunction. We recently discovered that synapses contain the necessary machinery to both synthesize and utilize lipid droplets, and that they normally constantly burn through these lipid droplets to sustain synapse function. Mutations in the key triglyceride lipase required to lipid droplet use are drivers of neurological disease, including intellectual disability. Similarly, we have recently uncovered a new role for neuromodulators at nerve terminals: in addition to directly controlling synapse function, they serve as signals to tell synapses to either store or use glycogen. Our aims to examine how difference cell biological machineries in synapses allow fuel switching and how perturbations in these machineries drive or heighten neurological disease states.

NIH Research Projects · FY 2024 · 1994-09

Faculty from two institutions, Weill Cornell Medicine ((WCM), formerly, Weill Cornell Medical College (WCMC)), and Memorial Sloan-Kettering Cancer Center (MSKCC), who share a single PhD program, are requesting funds to support an innovative and collaborative training program in cancer pharmacology. Our cancer pharmacology training grant/program (CPTG) includes an integrated set of training activities for PhD students and postdoctoral fellows. The strength and research diversity of the 24 faculty research advisors provide opportunities for research in a variety of areas, including the development of new cancer therapeutic agents (e.g. organic synthesis, monoclonal antibody technology, differentiation therapy, immunotherapies, & the screening of chemical libraries), the analysis of molecular mechanisms to identify new drug targets, exploration of how drugs act on cancer cells, cancer prevention, and clinical trials. This CPTG is unusual in that it features broad training ranging from molecular pharmacology to animal models of cancer and human clinical trials. Many faculty on the CPTG are physician-scientists who treat patients as well as perform research. The PhD program includes course work, three lab rotations, an admission to candidacy exam, thesis research, and a robust mentoring program. A major PhD course, Cancer Pharmacology (part of this program) represents a strong commitment of the 24 CPTG faculty to the training of students and fellows. Students and fellows present their research at the annual two-day Pharmacology Program retreat and at scientific meetings. Pre- and postdoctoral CPTG fellows attend weekly journal clubs and take courses related to cancer pharmacology. We are continuing to expand the successful Bench-to-Bedside, a course in drug development/entrepreneurship. Since the last competitive renewal, we established From Molecule to Prescription, a course taught by pharmacologists working in drug companies. We also started a course on biostatistics, bioinformatics, and quantitative biology. We actively use External and Internal Advisory Committees, plus a CARR (Committee for Admissions, Recruitment, & Retention). This CPTG has a number of strengths, most notably extremely large pools of well-qualified training grant-eligible applicants for both the predoctoral and postdoctoral positions; an expanding group of highly collaborative and talented CPTG faculty research advisors; a high productivity in terms of publications by trainees; and the tremendously vibrant and collaborative intellectual atmosphere in the tri-institutional research area. Thus, this CPTG will continue to provide PhD students and postdoctoral fellows with an in depth understanding of the interrelationships among research on the basic mechanisms of drug action, drug development, and clinical issues, producing the next generation of clinicians, clinician-scientists, and pharmacologists in basic research who will be well prepared to carry out independent research and work at the scientific frontier to understand, prevent, and treat cancer.

NIH Research Projects · FY 2026 · 1994-05

Project Summary/Abstract Many potent and effective broadly neutralizing antibodies (bNAbs) directed to the HIV-1 envelope glycoprotein (Env) trimer have been studied mechanistically and structurally. Combined, their epitopes now cover most of the external surface of Env. Passive immunization with bNAbs, optimally mixed to minimize viral escape, holds promise for controlling HIV-1 infection, prevent it, or even helping to cure it. Eliciting bNAbs by active immunization, however, remains problematic. Our overall long-term goal is to contribute to solving that major problem. We will develop techniques for quantifying concentrations, affinities, kinetics, and stoichiometry of bNAb binding in polyclonal sera from infected or immunized animals and humans. We will determine how these quantities change as germline (GL) responses mature into bNAbs. So far, we have used soluble, native-like SOSIP trimers to dissect or induce Ab responses. The recent emergence of mRNA vaccination, however, allows the design of full-length Env constructs, opening the possibility of presenting external bNAb epitopes located near the membrane while shielding C-terminal neo-epitopes at the base of soluble trimers. We will therefore make virus-like particles that mimic HIV-1 virions in size, membrane composition, Env density, and Env interactions with interior viral proteins. The kinetics and stoichiometry of bNAb binding to these full-length membrane-anchored trimers, with and without changes in the cytoplasmic tail, will be compared with binding to SOSIP trimers. We will also extend in-depth binding analyses to SOSIP trimers derived from a global panel of neutralization-resistant HIV-1 isolates. We will dissect binding kinetics, stoichiometry, induced conformational changes, and the heterogeneity of the interactions, thereby identifying binding characteristics that correlate with neutralization breadth. In silico analyses of how the midpoints and Hill slopes (h) of the neutralization curves relate to neutralization breadth, for both single bNAbs and combinations, will guide further experimental dissections of how binding properties mold cross-reactivity. We will develop assays for measuring entry-fusion fitness to define the relationship between viral resistance to bNAbs and the efficiency of receptor-facilitated entry. To achieve these goals, we propose three Specific Aims: Aim 1. Analyze bNAb binding and neutralization properties relevant to passive and active immunization. Aim 2. Determine how bNAb breadth and binding properties are interrelated. Aim 3. Dissect the relationship between entry fitness and escape from bNAbs. In summary, we seek to define how dynamic properties of Ab binding are linked to neutralization breadth. Such fundamental information may help improve both active and passive immunization strategies, which are highly relevant to public health.

NIH Research Projects · FY 2025 · 1990-03

Title: Postgraduate Research Fellowship in Mid- and Late-Life Mood Disorders PROJECT SUMMARY This is the 7th competing application of this T32 Research Fellowship Program in Mid- and Late-Life Mood Disorders, which has been offering multidisciplinary training for 30 years. This successful T32 has undergone continuous transformation in response to scientific developments, NAM mandates, the 2020 NIMH Strategic Plan Draft Priorities, the RDoc Project, and the evolving expertise of our faculty. The new T32 organizes its research training in a continuum in which our human neurobiology studies provide targets for our novel treatment development initiatives and our services research seeks to extend the quality and reach of mental health treatment in the community. The Program's strengths are: 1) The academic record of its trainees; the 13 fellows trained over the past 10 years received 3 K Awards, a 4th K Award received a priority score of 16 in the Study Section of March 2020, and coauthored 82 papers (41 first-authored); 2) Leadership in research training at a national level (PIs of the NIMH Research Career Institute in Mental Health of Aging and faculty of the NIMH Advanced Research Institute); 3) NIMH-funded faculty in studies ranging from molecular genetics, neuroimaging, clinical pharmacology, intervention development, and mental health services; 4) Cohesive organization of the Weill- Cornell Institute; 5) Ten Cornell pilot project programs; 6) Rich study populations and laboratory resources; 7) Databases available for secondary analyses and hypothesis generation by fellows; 8) Long and effective collaboration with investigators of Geriatric Medicine, General Internal Medicine, Services Research Program, Public Health, and Medical Ethics; and 9) Leadership in 8 multisite studies. The Program will be directed by funded investigators in clinical biology (F. Gunning), novel treatment development (G. Alexopoulos) and community studies (J.A. Sirey) with a strong record in research training and by an Executive Committee with expertise in molecular genetics, neuroimaging, treatment development, and diversity studies. We request support for 3 trainees, whose personalized training programs will be coordinated by a primary and a secondary mentor and specialized advisors to facilitate translation research. Beyond a Core Curriculum, we support our trainees in conducting their own studies, in preparing funding applications, and in publishing data-based papers.

NIH Research Projects · FY 2026 · 1989-01

Understanding the processes by which the brain transforms sensory input into representations that support decisions and actions is a central goal of systems neuroscience. Here, we undertake inter-related streams of psychophysical, computational, and theoretical studies to advance towards this goal. We focus on visual judgments of textural similarity and material properties, two related processes that are not only good model systems for this purpose, but also important for behavior. We characterize the perceptual representations in these domains and the transformations between them, ask whether canonical neural computations can account for these findings, and develop tools to analyze the characteristics of perceptual representations in general. To do this, we build on advances of the previous project period, which developed a predictively accurate model for visual texture discrimination. Human behavior, as captured by this model, was close to normative (sensitivities to local image statistics were matched to their informativeness in natural images) and the perceptual representation had a simple, Euclidean geometry. However, when texture was used for different tasks – suprathreshold similarity and grouping -- the perceptual representation was altered dramatically, implying top-down influences on how sensory information is represented and transformed. We hypothesize that this phenomenon is general, and that task-dependent transformations have geometries that correspond to recognized canonical neural computations. Here we pursue these ideas and their implications. In Aim 1A, we delineate the transformation from threshold representations of visual texture to suprathreshold representations of similarity, and in Aim 1B, how this representation is modulated by task demands (similarity vs. dis-similarity, comparisons in working memory, and grouping). In Aim 2, we examine visual judgments of material properties. Previous work shows, perhaps surprisingly, that these affordance judgments are driven by low-level visual features at specific spatial scales, and our preliminary results indicate that local image statistics play a major role. Aim 2A will characterize the visual estimation of material properties for multiple affordances. Aim 2B will determine the computations that relate suprathreshold judgments of similarity to the representation space of affordances. These aims are pursued in a novel geometric framework, motivated by several lines of evidence that Euclidean models may fall short. We consider a wide range of model classes for the representational spaces and the transformations between them, and apply innovative, rigorous tests based on the data we acquire. As the analytical tools are likely to be widely applicable, Aim 3 expands these developments and makes easily-used tools available to the community. We anticipate that the processes that we delineate at the algorithmic and computational levels in Aims 1 and 2 will reveal generalizable insights into the functional role of canonical neural computations in visual perception, and that the tool development and promulgation in Aim 3 will enable tests of these ideas in many modalities.

NIH Research Projects · FY 2026 · 1988-02

Cancer is the 2nd leading cause of death in the US. The advent of new treatments such as immunotherapy and targeted therapies have revolutionized the fight against cancer, and when combined with surgery, often result in significant positive therapeutic responses. Unfortunately, some tumor cells gain the ability to resist drug- and immune- therapies, which is often linked to their ability to metastasize. Indeed, metastasis ultimately underlies the majority of patient mortality by cancer. A major unmet need in oncology is the prediction and prevention of metastatic progression. Thus, understanding how tumor cells acquire metastatic potential and develop drug resistance is critical to identifying novel therapeutic options and improving patient outcomes. It is of critical importance to define the signaling mechanisms that contribute to altered growth, metabolism, motility and survival associated with metastasis. Our long-standing goal is to uncover the molecular consequences of Ras/ERK-MAP kinase signaling using biochemical, cell biological and genetic approaches in vitro and in vivo. We have provided the foundational studies revealing how subtle differences in ERK signal strength, location and duration are critical determinants of cellular outcomes. More recently, we demonstrated that different ERK isoforms promote different cell fates. Specifically, we found that different docking domains within ERK2, the CD domain and the DEF binding pocket (DBP), regulate different cellular outcomes, with ERK2 playing a major role in promoting the epithelial-to-mesenchymal transition (EMT) through DBP signaling. Additionally, this EMT-like phenotype was associated with increased motility, survival and metastasis in vivo and in vitro. Understanding these mechanisms are part of the long-term goal of our basic research efforts to discover new potential targets and identify new biomarkers, and to help resolve this currently unmet clinical need of targeting the metastatic process. Thus, this grant application proposes to mechanistically investigate underexplored areas associated with EMT and metastatic progression, taking advantage of discoveries made during the previous 30+ years investigating the ERK pathway in my laboratory. Our goals include an investigation into: (i) the regulation and role of H3.3 histone chaperones and H3.3 modifications, (ii) the role SP1/EGR1-downregulated genes and their characterization as new metastasis suppressors, such as CHAF1b and MCEE; (iii) the function of massive reorganization of endomembrane trafficking, lysosome and autophagosome function and the unexplored regulation and function of various plasma and lysosome membrane transporters in the maintenance of cancer stem cell properties, invasion, survival and chemoresistance during cancer progression and metastasis. In conclusion, there is an essential need for greater understanding of the mechanisms associated with metastatic behavior. Our expectations are that successful completion of the proposed work will impact cancer therapies through identification of new biomarkers and novel drug targets that will yield small molecules that target the invasiveness and survival of aggressive cancers.

NIH Research Projects · FY 2025 · 1986-12

Project Summary The Pediatric Scientist Development Program (PSDP) remains committed to building a diverse next generation of pediatrician scientist leaders, including: (a) to recruit diverse pediatric fellows whose outstanding potential for a successful investigative career can be developed in an intensively mentored setting and (b) to expand and diversify the pipeline of superbly trained pediatric physician-scientists, who will catalyze cutting-edge discoveries in child health and lead the pediatric departments of the future. Despite the successful history of this program, the ongoing limited diversity of pediatrician scientist leaders and the changing landscape of health care, academic medicine, and biomedical research requires ongoing modifications. The innovative aspects of this resubmission include: 1. Sustain our diversity recruitment pipeline that includes a successful re-focus of the AMSPDC Frontiers in Science (FIS) resident research experience as a diverse candidate pool and partnership with organizations that train diverse academic pediatricians, to maintain a goal of ≥25% of applicants and >50% scholars from underrepresented in medicine (URiM) backgrounds in this grant cycle 2. Harness the power of our robust, alumni network for near-peer mentoring and pipeline enhancement 3. Co-sponsorship of fellows by foundations focused on child health research for general pediatric and disease-specific research training 4. Partnerships with complimentary training programs to aid PSDP fellow interdisciplinary training and networking 5. Added flexibility for the clinical training component to focus on the disease area of research, building the desired synergy in research and clinical training 6. New funding strategy that will support applicant pool flexibility and the fellow-to-faculty transition 7. Iteratively informed hybrid curriculum with “flipped classroom” interactive components, and a focus on diversity and health equity aspects of pediatric research 8. Virtual platforms to enhance recruitment, selection, and professional development delivery We project to train 55 PSDP Scholars in subspecialty fellowships (2023-2028). Of the 55 Scholars, 32 Scholars will be funded by the NIH (includes one slot for HIV-related work co-funded by the Office of AIDS Research). We will also have one intramural slot funded by the NICHD Division of Intramural Research. The PSDP will build on lessons of more than 39 years to strengthen our national network, evolve career development emphases and novel educational approaches, diversify the pediatric research workforce pipeline, and nurture the next generation of diverse pediatric physician-scientists who will generate innovations children's health.