NYU Cancer Health Disparity SPORE
New York University
Principal Investigator(s):
Jiyoung Ahn, PhD
- Principal Investigator(s) Contact Information
- Overview
- Project 1: Role of the Oral Microbiome and Tumor Microenvironment in Disparities in Squamous Cell Head and Neck Cancer Development
- Project 2: Role of Gut Microbiome and Tumor Microenvironment in Disparities in Colon Cancer Outcomes
- Administrative Core
- Biospecimen Procurement and Utilization Core
- Biostatistics and Bioinformatics Core
- Developmental Research Program
- Institutional SPORE Website
Principal Investigator(s) Contact Information
Jiyoung Ahn, PhD
Associate Director for Population Science, Perlmutter Cancer Center
Professor of Population Health
NYU Langone Health
180 Madison Ave, #414
New York, NY 10016
(212) 263-3390
Overview
Orodigestive tract (ODT) cancers, which account for 32% of cancer deaths in the US, exhibit striking racial disparities in incidence and mortality burdens. Our central hypothesis is that the human microbiome contributes to ODT cancer disparities through biologic interaction of the microbiome with the host in ODT oncogenesis. The overall objective of the NYU Cancer Health Disparity (CHD) SPORE is to develop a comprehensive translational research program to identify, understand and control the microbiota that account for orodigestive tract (ODT) cancer disparities.
- Project 1 will focus on the relationship of the oral microbiome to racial and socioeconomic disparities in the incidence of head and neck cancer, by means of a prospective case-control study nested within 3 large highly diverse US cohorts.
- Project 2 will focus on the gut microbiome and Black and White racial disparities in tumor recurrence in colon cancer patients who received adjuvant chemotherapy.
Our research will be strongly supported through shared Cores: (A) Administrative, (B) Biospecimen Procurement & Utilization, and (C) Biostatistics and Bioinformatics. This SPORE also supports a Developmental Research Program to support innovative translational concepts.
The NYU CHD SPORE will provide new knowledge on specific human microbiota that contribute to ODT cancer disparities and will advance our understanding of the functional consequences of these microbiota in ODT oncogenesis. The knowledge gained from the proposed research in the SPORE will transform current clinical practice by identifying high risk groups for ODT cancer in minority populations, that will provide the scientific basis for developing microbially-based personalized prevention, clinical decision tools, and prophylactic interventions to address ODT cancer disparities.
Project 1: Role of the Oral Microbiome and Tumor Microenvironment in Disparities in Squamous Cell Head and Neck Cancer Development
Project Co-Leader:
Richard B. Hayes, DDS, PhD, MPH (Basic)
Squamous cell head and neck cancer (SCHNC) results in extensive physical disfigurement, and leads to ~40% 5-year mortality; thus its prevention is extremely important. Blacks and people with low socioeconomic status (SES) have a high burden of SCHNC. We hypothesize that the oral microbiota contribute to the racial and socioeconomic disparities in SCHNC. Oral bacteria and fungi can cause epithelial cell DNA damage by carcinogen metabolism, and some of these somatic mutations may be critical for SCHNC carcinogenesis. Bacteria and fungi may also promote carcinogenesis through immunogenic stimulus for innate immune system response via pattern recognition receptors, leading to immune cell recruitment and an altered tumor immune microenvironment. Thus, a microbial role in SCHNC development and the shaping of the tumor mutational and immune microenvironment is of great potential importance in the pathogenesis of SCHNC. Our preliminary data show that Blacks and individuals with low socioeconomic status exhibit lower overall oral microbiome diversity, particularly characterized by lower abundance of bacteria Corynebacterium and Kingella; we had previously reported that low abundance of these two bacteria is also associated with increased risk of SCHNC development. Our work further points to involvement of oral bacteria in carcinogen metabolism, with potential impact on tumor mutational load and immune infiltration. While this preliminary data supports our hypothesis, no studies have examined the comprehensive relationship between the oral microbiome, tumor microenvironment, and SCHNC in racial and socioeconomic minority populations.
Our overall goal is to generate important biologic insights about oral microbial factors that underlie racial and socioeconomic disparities in SCHNC development. In this research, we expect to identify specific oral microbiota contributing to these disparities and to identify the tumor microbiota that influences host tumor mutation burden and the tumor immune microenvironment. This project will help to achieve SCHNC health equity by generating novel information from diverse population groups about the role of the oral microbiome in SCHNC development and pathogenesis. Knowledge gained may improve our ability to identify people at high risk of SCHNC, particularly in underserved minority groups. The new information may further lead to novel prevention and therapeutics approaches that exploit microbially-driven immune responses in SCHNC.
Project 2: Role of Gut Microbiome and Tumor Microenvironment in Disparities in Colon Cancer Outcomes
Project Co-Leaders:
Jiyoung Ahn, PhD (Basic Co-Leader)
Paul Oberstein, MD (Clinical Co-Leader)
Deirdre Cohen, MD (Clinical Co-Leader)
U.S. Blacks have the highest mortality rate of colorectal cancer of any ethnic group in the country. To achieve colon cancer health equity, it is critical to determine the underlying biological factors associated with poorer colon cancer outcomes in Blacks, which could lead to tailored prevention and intervention approaches.
The gut microbiota may play an important biologic role in racial disparities for colon cancer outcomes. Increasing evidence indicates that the gut microbiota influences innate and adaptive immune function in the tumor microenvironment. The tumor immune microenvironment is critical for the detection and destruction of nascent tumor cells. Our preliminary data suggest that healthy Blacks have a significantly different gut microbiome compared to Whites; importantly, we showed that these gut bacteria are further altered in colon cancer patients, supporting our hypothesis. Our animal experiments further suggest that gut bacteria modulate tumor immune microenvironment and affect the efficiency of cancer response to therapy. However, no studies have examined the relationship between the broader human microbiome, tumor immune microenvironment, and outcomes of colon cancer in the comparative research setting with Blacks and Whites.
Our overarching goal is to achieve colon cancer health equity, by elucidating gut microbial factors associated with poorer colon cancer outcomes in Blacks. Our specific aims are 1) to identify gut bacteria associated with racial disparity in colon cancer and its recurrence, using full genome shotgun sequencing microbiome assay in Black and White colon cancer patients (Stage I-III); 2) to determine how the immune system mediates the microbiome’s effect on colon cancer disparity, using immunophenotyping assay, from 30-parameter flow cytometry, and neoantigen load, from whole exome sequencing, in tumors of Black and White colon cancer patients. This first microbiome study of colon cancer disparities will comprehensively investigate the gut microbiome and its role in shaping the tumor immune microenvironment. This project will help to achieve colon cancer health equity by generating novel information about the role of the microbiome in colon tumorigenesis and progression. Knowledge gained from this study may improve our ability to identify people at high risk of recurrence, particularly in Blacks. The new information may further lead to the development of tailored approaches to prevention and therapeutics that exploit microbially-driven immune responses in colon cancer.
Administrative Core
Core Director:
Jiyoung Ahn, PhD
Core A is charged with facilitating communication and sustaining integration among the SPORE members and projects, as well as providing efficient support services for all of the SPORE components, in order to maximize synergy in achieving our translational research goals.
Biospecimen Procurement and Utilization Core
Core Directors:
Richard B. Hayes, DDS, PhD, MPH
Andre Moreira, MD
Core B contributes to the SPORE’s translational research goals by providing NYU CHD SPORE investigators with high-quality, clinically annotated biospecimens. Core B will capitalize on, and extend, the existing infrastructure and capabilities created through the NYU CHD Biorepository, to include 1) the NYC community based FAMiLI cohort and 2) the ODT cancer cohort. Core B will support the NYU CHD SPORE in three critical ways: 1) It will maintain and grow the biospecimen resources and related data; 2) It will provide pathology and molecular services (e.g., nucleic acid extraction and immune cell isolation) to strengthen the SPORE's translational research aims; and, 3) It will build on its existing systems, serving as the coordinating unit to receive, process, prioritize, and distribute biospecimens and corresponding data to SPORE project investigators.
Biostatistics and Bioinformatics Core
Core Directors:
Huilin Li, PhD
Kelly Ruggles, PhD
Core C contributes to the SPORE’s translational research by providing biostatistics and bioinformatics support and collaboration for Research Projects, DRPs, and Core B. Core C will provide consultation on study design and planning, implementation, statistical analysis, and interpretation of results, and will maintain analytic datasets. The Core will also develop innovative statistical design and analysis methods, novel informatics methods, and provide publicly available algorithms for use by other cancer researchers.
Developmental Research Program
Program Director:
Chau Trinh-Shevrin, DrPH
The developmental research program supports innovative pilot projects in cancer health disparities and encourages translational proposals for understanding the biologic and social factors that cause disparities of orodigestive tract cancers.