Perspective: Incoming Class of Junior Faculty Awardees

ACG’s 2021 Junior Faculty Development Awardees Share Thoughts on Their Research and Career Focus

Eileen Carpenter, MD, PhD

University of Michigan The Tumor Immune Microenvironment and Pancreatic Cancer Chemoresistance

This year I am starting as faculty at the University of Michigan, specializing in pancreatic diseases. I recently completed my residency and GI fellowship at Michigan as part of their physician-scientist training program, with funding from a T32 research grant and an ACG clinical research award.

Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related death in the U.S. Human studies have been challenging due to fresh biospecimen acquisition, patient heterogeneity, and a diverse tumor microenvironment. In my proposal, we address these obstacles by exploiting endoscopic opportunities to obtain specimens during diagnostic biopsy (treatment-naïve) and fiducial placement for radiotherapy (post-treatment). With generous support from the ACG Junior Faculty Development Award, I will test the hypothesis that chemotherapy alters the tumor microenvironment in pancreatic cancer through reprogramming of the local and systemic immune system, which can be exploited to uncover mechanisms of therapy resistance. In Aim 1, we will utilize single cell RNA sequencing and mass cytometry on longitudinally matched patient biospecimens to define immune signatures of tumor response to chemotherapy in patient tumors and peripheral blood with the goal of correlating signatures to disease outcomes. In Aim 2, we will use an in vitro all-human patient derived co-culture system of tumor organoids and peripheral myeloid cells to dissect the immune-epithelial crosstalk responsible for therapy resistance.

Having decided early on that I would devote my career to researching pancreatic cancer, approaching this disease from the perspective of a gastroenterologist has been incredibly rewarding as both a researcher and a physician. I am extremely grateful for the ACG in supporting my proposal, which will not only serve as a launching pad in my path to independence, but also support the development of an invaluable comprehensive dataset of the microenvironment in pancreatic cancer and provide new immunotherapeutic targets in this deadly disease. health disparities on patient outcomes, particularly those with cancer. During that time, I was inspired to pursue a career combining a clinical practice focused on hepatology and disparities-focused research.

Men bear a disproportionate burden of HCC, with incidence and mortality rates 2 – 8 times higher than women observed over the past 50 years across all regions of the world and all racial/ethnic groups. Despite this consistent finding, there are limited data identifying the factors underlying this disparity and existing studies have often failed to distinguish the distinct paradigms of sex- (i.e., biologic) and genderrelated (i.e., environmental or behavioral) factors. With the generous support from the ACG Junior Faculty Development Award, I will complete two complementary research projects and training aims that will prepare me to comprehensively evaluate the magnitude and mechanisms of sex and gender disparities in HCC. Guided by a proven multi-level framework for studying cancer disparities, I will leverage unique data and infrastructure from three large cohorts. My first aim is to estimate the association between sexrelated factors and HCC risk in two well-characterized prospective cohorts comprised of >4,000 patients with cirrhosis. The second aim will use identify genderrelated behavioral and healthcare utilization factors associated with HCC survival using patient-reported data from surveys and structured interviews. Data generated from this project will fill important gaps in our understanding of the influence of sex and genderrelated factors on HCC risk and survival and serve as the groundwork for an eventual R01 grant application. It is a great honor to receive this award; the skills I will acquire through completion of the research and training aims will facilitate my transition to an independent research career focused on reducing health disparities in patients with liver disease and HCC.

Nicole Rich, MD

University of Texas Southwestern Sex and Gender Disparities in Hepatocellular Carcinoma Incidence and Prognosis

I am an Assistant Professor of Medicine and transplant hepatologist in the Division of Digestive and Liver Diseases at UT Southwestern. The core focus of my research, as a clinical researcher, is to understand and identify mechanisms contributing to racial/ethnic, sex/ gender, and socioeconomic disparities among patients with chronic liver disease and hepatocellular carcinoma (HCC). I received training in gastroenterology and advanced/transplant hepatology through fellowships at UT Southwestern, and completed a Master of Science in Clinical Science (MSCS) degree in 2020. During fellowship, I completed dedicated research training on the NIH T32 training grant under the mentorship of Dr. Amit Singal and Dr. Jorge Marrero, both internationally recognized experts in the field of HCC early detection, surveillance and biomarkers. As a trainee caring for uninsured and underinsured patients at Parkland Health & Hospital System, the safety-net system of Dallas County, I regularly witnessed the adverse impact of