This federal Project Grant award from the National Cancer Institute (CFDA 93.396 - Cancer Biology Research) provides $646,739.00 to Cedars-Sinai Medical Center to investigate the molecular mechanisms by which obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) promote liver metastasis in gastrointestinal cancers such as colorectal and pancreatic ductal adenocarcinoma. The key focus is on understanding the differential roles of extra-tumoral and intra-tumoral hepatic...
This Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), provides $243,590 to the University of Chicago to investigate the role of the protein BNIP3 in regulating lipid homeostasis in the liver. The goal is to define the mechanisms by which BNIP3 influences the accumulation of lipid droplets, which is a key factor in the development of non-alcoholic...
This federal Project Grant award, funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), will support research at the Pennington Biomedical Research Center to examine the role of the mitochondrial protein SLC25A25 in the onset and progression of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH)....
This Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (CFDA 93.847 - Diabetes, Digestive, and Kidney Diseases Extramural Research) supports research to understand the underlying mechanisms of non-alcoholic steatohepatitis (NASH), a liver disease that is expected to become the leading indication for liver transplantation. The $172,060 award to The General Hospital Corporation (doing business as Massachusetts General Hospital) aims to investigate how...
This Project Grant award from the National Cancer Institute (CFDA 93.398 - Cancer Research Manpower) provides $100,923 to Rockefeller University to identify mechanisms of resistance to SLC6AB inhibition in colorectal cancer liver metastasis. The key objectives are to: 1) establish the significance and mechanisms of the leukemia inhibitory factor receptor (LIFR) axis in promoting chemotherapy resistance in ovarian cancer cells, and 2) define the mechanisms by which hypoxia and the LIFR axis...
This Project Grant award from the National Cancer Institute's Cancer Research Manpower program (CFDA 93.398) is supporting research to develop novel inhibitors of the CYP8B1 protein, which plays a key role in the development of obesity-associated hepatocellular carcinoma (HCC). The $213,284 award to the Beckman Research Institute of the City of Hope will fund two aims: 1) Determining the role of CYP8B1 in obesity-associated HCC using mouse models, and 2) Performing chemical modifications and...
This federal Project Grant award from the National Cancer Institute (CFDA 93.398 Cancer Research Manpower) provides $165,883 to Brigham & Women's Hospital Inc. (a subsidiary of Partners Healthcare System Incorporated) for a 2-year research project titled "Inflammation and Hepatocellular Carcinoma: A Multiomics Approach to Improve Early Detection, Causal Inference, and Lifestyle Based Prevention." The project aims to leverage epidemiological data and advanced multi-omics analytics...
This Project Grant award from the National Cancer Institute (CFDA 93.398 Cancer Research Manpower program) provides $192,240 in funding to the University of Texas MD Anderson Cancer Center to conduct research on the functional contribution of extracellular vesicles in pancreatic cancer. The research aims to: (1) investigate the functional impact of cancer cell extracellular vesicles on pancreatic cancer initiation and progression, (2) evaluate the role of cancer cell extracellular vesicle...
The National Cancer Institute (CFDA 93.396 - Cancer Biology Research) awarded Loyola University of Chicago a $461,844 project grant titled "Hyperpolarized 13C Metabolic Imaging of Tumorigenesis in the Liver". The objective is to use novel hyperpolarized 13C probes to image glycolysis, a critical pathway in hepatocellular carcinoma (HCC) development, and establish in vivo imaging biomarkers to assess altered liver metabolism during HCC progression. The project aims to synthesize a...
This Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), will support research to investigate how obesity impacts the migration of immature neutrophils and the effects on hematopoietic stem and progenitor cells (HSPCs), metabolism, and systemic inflammation. The total award amount is $146,922 and the project period runs from June 23, 2025 to March 14,...
THE CROSSTALK BETWEEN OBESITY-INDUCED FATTY LIVER AND LIVER METASTASIS - PROJECT SUMMARY/ABSTRACT CANDIDATE: AS A POSTDOCTORAL FELLOW IN DR. SCOTT LOWE'S LAB AT MSKCC, MY RESEARCH FOCUSES ON THE CONTRIBUTION OF OBESITY-INDUCED NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD), PARTICULARLY HEPATIC LIPID ACCUMULATION, TO LIVER METASTASIS FROM PANCREATIC DUCTAL ADENOCARCINOMA (PDAC). MY LONG-TERM GOAL IS TO ESTABLISH AN INDEPENDENT RESEARCH PROGRAM THAT AIMS TO DISSECT THE INTERACTIONS BETWEEN OBESITY/NAFLD AND METASTASIS, WITH THE ULTIMATE GOAL OF EXPLOITING THIS KNOWLEDGE FOR THERAPEUTIC BENEFIT. THE PROPOSED RESEARCH WILL FORM A SOLID FOUNDATION, ON WHICH I CAN ESTABLISH MY OWN RESEARCH GROUP BY THE END OF THE K99 PHASE. RESEARCH: LIVER IS A FREQUENT METASTATIC SITE FOR MANY CANCERS INCLUDING PDAC, AND LIVER METASTASIS IS TYPICALLY ASSOCIATED WITH POOR PROGNOSIS. OBESITY-ASSOCIATED NAFLD IS THE MOST PREVALENT CHRONIC LIVER DISEASE THAT AFFECTS ~25% OF THE POPULATION WORLDWIDE, AND WILL BECOME A PREDOMINANT FACTOR IN SHAPING THE NICHE FOR METASTATIC CANCERS. HOWEVER, HOW CANCER MECHANISTICALLY TAKES ADVANTAGE OF THE LIPID-RICH AND INFLAMMATORY ENVIRONMENT OF NAFLD REMAINS LARGELY UNKNOWN. MY EARLY POSTDOCTORAL WORK SHOW THAT LIVER METASTASIS FREQUENTLY CO-OCCURS WITH HEPATIC LIPID ACCUMULATION IN PATIENTS, AND FATTY ACID IS A CAUSAL DRIVER OF PDAC LIVER METASTASIS IN MOUSE MODELS OF NAFLD. MOREOVER, IN OBESE MICE, THE KEY LIPOLYSIS ENZYME IS UNCONVENTIONALLY ELEVATED IN HEPATOCYTES ADJACENT TO METASTASES, WHICH ACCUMULATE FATTY ACID CATABOLITE B-HYDROXYBUTYRATE (BOHB) AND UPREGULATE INTERFERON-G (IFNG) RESPONSES. THIS PROPOSAL WILL TEST THE HYPOTHESIS THAT METASTASIS INDUCES LIPOLYSIS IN NEIGHBORING HEPATOCYTES TO PROVIDE FATTY ACIDS, WHICH CREATES A MULTIFACETED PRO-METASTATIC PROGRAM. I WILL LEVERAGE FUNCTIONAL GENETICS IN MOUSE MODELS TO INTERROGATE LIPOLYSIS IN THE NICHE HEPATOCYTES (AIM 1), AND TO DETERMINE THE CONTRIBUTIONS OF FATTY ACID-BOHB TO EPIGENOME (AIM 2) AND IFNG SIGNALING TO THE IMMUNE NICHE (AIM 3) IN NAFLD-DRIVEN METASTASIS, WITH SPATIAL ANALYTICS TO VALIDATE THESE RESULTS IN HUMAN SAMPLES. THESE STUDIES WILL ILLUMINATE THE MECHANISMS THAT DRIVE LIVER METASTASIS IN OBESITY AND NAFLD, WHICH COULD INFORM NEW STRATEGIES FOR THERAPEUTIC INTERVENTION IN A GROWING POPULATION OF PATIENTS. ENVIRONMENT: MSKCC PROVIDES AN IDEAL ENVIRONMENT FOR ME TO ACCOMPLISH MY TRAINING AND RESEARCH GOALS, AND SUCCESSFULLY TRANSITION TO AN INDEPENDENT FACULTY POSITION AT AN ACADEMIC INSTITUTION. MY MENTOR DR. LOWE IS A WORLD LEADER IN CANCER BIOLOGY, WITH EXPERTISE ON CANCER GENETICS AND MOUSE MODELS. IN ADDITION, I HAVE ASSEMBLED AN ADVISORY COMMITTEE OF ESTABLISHED SCIENTISTS WITH RELEVANT EXPERTISE AND STRONG COMMITMENT TO MENTORING (DRS. FARESE, LI, AND SHERMAN). TOGETHER, ALL MENTORS WILL SUPPORT MY TRANSITION TO INDEPENDENCE BY PROVIDING VALUABLE RESEARCH EXPERIENCE AND CAREER GUIDANCE. WITH THE COLLABORATIVE ENVIRONMENT AND BROAD SPECTRUM OF RESOURCES AT MSKCC, THIS SUPPORT NETWORK CREATES OPTIMAL CONDITIONS FOR THE SUCCESSFUL COMPLETION OF THE PROPOSED RESEARCH AND CAREER DEVELOPMENT PLANS.