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Last Updated: 09/10/21

University of Chicago Interdisciplinary Cancer Health Disparities SPORE

The University of Chicago

Principal Investigator(s):

Olufunmilayo Olopade, MD
Olufunmilayo Olopade, MD

Dezheng Huo, PhD
Dezheng Huo, PhD

Rita Nande, MD
Rita Nande, MD

Principal Investigator(s) Contact Information

Olufunmilayo Olopade, MD
Walter L. Palmer Distinguished Service Professor of Medicine & Human Genetics
Associate Dean for Global Health
The University of Chicago
5841 S. Maryland Avenue MC 2115
Chicago, IL 60637
(773) 702-1632

Dezheng Huo, PhD
Professor of Public Health Sciences
Professor of Medicine
The University of Chicago
5841 S. Maryland Avenue MC2000
Chicago, IL 60637
(773) 702-2453

Rita Nande, MD
Associate Professor of Medicine
Director, Breast Oncology Program
The University of Chicago
5841 S. Maryland Avenue MC2115
Chicago, IL 60637
(773) 702-6149

Overview

The University of Chicago has active clinical, basic and population science programs and thriving translational research programs. The goal of this SPORE is to reduce global disparities in cancer outcomes by developing the platform to apply novel approaches to the prevention, diagnosis and treatment of cancers exhibiting disparities in incidence or outcomes among US Minority populations. We leverage our institutional strengths in emerging new fields of science including bioinformatics, genomics therapeutics, human genetics, immunology, medical oncology and statistical genetics. These advantages, together with our location in the ethnically diverse south side of Chicago and our exciting new partnerships in the UChicago Institute for Translational Medicine, make this a truly unique SPORE program.

Our goals are in two interrelated thematic areas with specific aims, Aim 1) To find novel ways to make chemotherapy more effective for patients with aggressive cancers. Project 1: Integrating Tumor Genomic and Gut Microbiome Analyses to Close Breast Cancer Mortality Gap will use a highly innovative approach to extend our understanding of the biologic basis of breast cancer progression by performing deep whole exome sequenicng (WES) of 500 well-phenotyped tumors to identify somatic mutation signatures. This intimate association between the gut mucosa and the resident microbial community facilitates immune responses against invading pathogens and tolerance to beneficial microbes and may influence tumor progression and how patients respond to chemotherapy. We will recruit 750 new breast cancer patients and collect stool for Microbiome Wide Association Study in 140 patients receiving neoadjuvant chemotherapy to determine whether fecal microbial biomarkers are predictive of response to neoadjuvant chemotherapy;

Aim 2) To personalize risk prediction for prevention and treatment of aggressive cancers. Project 2-Personalized Risk-based Imaging Surveillance Model (PRISM) for High Risk Women will examine whether ethnic specific Polygenic Risk Score (PRS) can stratify women into risk categories and subsequently used in the clinic to personalize culturally tailored risk-reducing interventions. We will test the hypothesis that state-of-the-art genomic testing combined with state-of-the-art Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) techniques can comprehensively characterize early breast cancers, and provide effective and affordable strategies for risk adapted management of mutation carriers in diverse populations.

Project 1: Integrating tumor genomic and gut microbiome analyses to close breast cancer mortality gap

Project Co-Leaders:
Olufunmilayo Olopade, MD (Clinical Science Co-Leader)
Rita Nanda, MD (Clinical science Co-Leader)
Dezheng Huo, PhD (Basic Science Co-Leader)

The primary objective of project 1 is to find novel ways to make chemotherapy more effective for patients with aggressive cancers. Finding new ways to optimize chemotherapy can improve outcomes for aggressive breast cancers that disproportionately affect women of African ancestry and promote health equity. Disparity in cancer outcomes is multifaceted, but for breast cancer, several important sets of factors appear to collide to create the “perfect storm” leading to the mortality gap. Differences in tumor biology, genomics and health care delivery patterns contribute to breast cancer mortality gap between white women of European ancestry and black women of African ancestry in the US. Beyond interventions to improve quality of care, there is an urgent call for innovative research focused on biologic and genomic differences contributing to mortality gap so that cancer treatments can be tailored to the needs of each patient to personalize care.

Project 1 will use a highly innovative approach to extend our understanding of the biologic basis of breast cancer progression by performing deep whole exome sequenicng (WES) of 500 well-phenotyped tumors to identify somatic mutation signatures. The intestinal tissue is an immune organ with lymphatic and resident specialized immune cells that provide constant surveillance of gut microbiome. This intimate association between the gut mucosa and the resident microbial community facilitates immune responses against invading pathogens and tolerance to beneficial microbes and may influence tumor progression and how patients respond to chemotherapy. We will recruit 750 new breast cancer patients and collect stool for Microbiome Wide Association Study in 140 patients receiving neoadjuvant chemotherapy to determine whether fecal microbial biomarkers are predictive of response to neoadjuvant chemotherapy. In an expansion of these studies, we will test whether combining immunotherapy with chemotherapy can close the mortality gap between women of European and African ancestries participating in cancer immunotherapy trials.

Project 2: Personalized risk-based imaging surveillance model (PRISM) for high risk women

Project Co-Leaders:
Olufunmilayo Olopade, MD (clinical science co-leader)
Dezheng Huo, PhD (basic science co-leader)
Gregory Karczmar, PhD (basic science co-leader)
Deepa Sheth, MD (clinical science co-leader)

The primary objective of project 2 is to personalize risk prediction for prevention and treatment of aggressive cancers. Personalizing risk prediction can bring us closer to population risk stratification and personalized screening. Critical obstacles to early detection and prevention of breast cancer in diverse populations include: 1) lack of clinically validated risk prediction tools for population risk stratification in underserved non-European ancestry groups who stand to benefit the most from risk reducing interventions; and 2) slow implementation and dissemination of innovations in Imaging Science to community practices. This project will examine whether ethnic specific Polygenic Risk Score (PRS) can stratify women into risk categories and subsequently used in the clinic to personalize culturally tailored risk-reducing interventions. We will test the hypothesis that state-of-the-art genomic testing combined with state-of-the-art Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) techniques can comprehensively characterize early breast cancers, and provide effective and affordable strategies for risk adapted management of mutation carriers in diverse populations. Successful development of clinically useful ethnic specific PRS model and implementation of inexpensive MRI methods will impact large numbers of women at risk of developing “lethal” forms of breast cancer at young ages in the US, which is currently estimated at nearly 26,000 triple negative breast cancers annually, and will also impact global cancer control efforts.

Administrative Core

Core Directors:

Olufunmilayo Olopade, MD (Core Director)
Rita Nanda, MD (Co-Core Director)
Dezheng Huo, PhD (Co-Core Director)

The Admin Core will provide overall oversight of all SPORE planning activities including research projects and cores, maintain authority and responsibility for all fiscal and budgetary matters, facilitate communication throughout the SPORE program, provide support for SPORE advocates within the Internal Advisory Committee, sustain ongoing collaborative projects, identify new opportunities for Inter-Spore Collaborations and public-private partnerships and ensure compliance with all institutional, governmental and NCI-specific regulations and requirements.

Biospecimen Pathology Core

Core Director:
Mark Lingen, DDS, PhD

The Biospecimen Pathology Core (BPC) plays a critical role in the effective procurement, pathologic characterization and analysis of human biospecimens. The core also aims to establish physiologically relevant cost-effective preclinical model for genomic, functional and drug screening studies focusing on breast cancer disparities. Both BPC components are vital for the translational research efforts within the proposed SPORE projects and for the collaborative projects from other institutions.

Genomics, Analytic and Informatics Core

Core Director:
Ted Karrison, PhD

The Genomics, Analytics and Informatics Core (GAIC) will provide support for the collection, management, integration, and analysis of data generated from all SPORE Planning Grant projects, including providing the computing and statistical infrastructure needed for development of a fully developed SPORE application upon completion of the planning grant. The core will be comprised of a team with expertise in bioinformatics and biostatistics, and will be responsible for providing technical support for genomic studies, collaborating on study design and statistical analyses, assisting in the analysis and interpretation of microbiome data, and providing cutting edge informatics tools. The core will work collaboratively with investigators from each of the main projects, the Developmental Research Program (DRP), and the Biospecimen and Pathology Core (BPC) to develop and maintain a data management system to facilitate data collection, integration, and sharing of data among all investigators, projects, and cores, and provide the expertise needed to statistically analyze, interpret, and report the results.

Developmental Research Program

Program Director:
Kay Macleod, PhD (Director)
Lucy Godley, MD (Co-Director)

In order to enable SPORE investigators to rapidly develop new research opportunities, which could translate into early benefits for breast cancer patients, and to allow for exploration of new techniques which may require substantial efforts but which are nevertheless not ready for full-scale multi-year research funding.

Institutional SPORE Website

https://www.uchicagomedicine.org/cancer/research/research-initiatives/cancer-disparities/breast-cancer-spore