Sylvan C. Baca, MD, PhD
Project title
"Epigenetic drivers of resistance to novel therapies for bladder and kidney cancer"
Promising new treatments for cancers of the bladder and kidney have been developed, but, as with many cancer therapies, tumors eventually develop resistance. Research has shown that cancer cells resist treatment in part via epigenetic changes—those that do not affect the DNA sequence itself but turn important genes on or off, allowing cancers to survive under therapeutic stress. Dr. Baca is using novel techniques to study the epigenomes of cancer cells from blood samples. His goal is to understand how changes in the epigenomes of bladder and kidney cancers lead to treatment resistance. This knowledge will enable the design of better treatments and drug combinations that will benefit patients with metastatic bladder or kidney cancers.
Institution
Dana-Farber Cancer Institute
Sponsor(s) / Mentor(s)
Toni K. Choueiri, MD
Cancer type
Kidney and Bladder
Research area
Epigenetics
Award Program
Clinical Investigator
Pavan Bachireddy, MD
Project title
"Immune evasive circuits that define MRD progression in myelodysplastic syndrome"
A major cause of relapse after therapy is the persistence of measurable residual disease (MRD) cells—cancer cells that remain after treatment and eventually spread. Due to technical and logistical challenges in accessing and analyzing MRD cells, the molecular and cellular pathways that enable MRD progression remain poorly understood. Dr. Bachireddy will use innovative molecular tools to analyze tissue samples from blood cancer patients at a single-cell level to unlock insights into MRD progression. Using cutting-edge machine learning approaches, he will identify immunosuppressive mechanisms that may be targeted to halt MRD progression. Beyond these blood cancers, he aims to reveal organizing principles of MRD progression that are relevant across human cancers.
Institution
The University of Texas MD Anderson Cancer Center
Sponsor(s) / Mentor(s)
Jeffrey J. Molldrem, MD
Cancer type
Blood
Research area
Tumor Immunology
Award Program
Clinical Investigator
Andrew L. Ji, MD
Project title
"Dissecting spatial crosstalk in squamous cell carcinoma arising in organ transplant recipients"
Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in the U.S. While most cases are caught early and cured with excision, this cancer is more aggressive in the organ transplant recipient (OTR) population, with higher rates of recurrence and metastasis. Treatment options are severely limited in these cases. OTRs require immunosuppression, which is linked to cSCC aggression, but the underlying molecular and cellular mechanisms are poorly understood. Dr. Ji has discovered an invasive cSCC subpopulation that communicates with non-malignant cell types in the tumor’s environment. By profiling OTR tumors using cutting-edge single-cell and spatial technologies, he aims to better understand how this harmful subpopulation emerges in the immunosuppressed setting, aided by crosstalk with these neighboring cells. His goal is to develop strategies for disabling invasion and improving treatment of cSCC in both OTRs and advanced cases in the general population.
Institution
Icahn School of Medicine at Mount Sinai
Sponsor(s) / Mentor(s)
Miriam Merad, MD, PhD
Cancer type
Skin
Research area
Genomics
Award Program
Clinical Investigator
Benjamin A. Nacev, MD, PhD
Project title
"Understanding and targeting chromatin reorganization in ATRX deficient sarcomas"
Sarcomas are a family of tumors for which there are few targeted treatments and outcomes are poor once the cancer has metastasized. Many sarcomas harbor recurrent mutations in proteins, known as epigenetic regulators, that control which genes are expressed and when. Among the regulators most frequently impacted is ATRX, which condenses regions of DNA into tightly packaged chromatin that cannot be accessed for transcription, effectively “silencing” these genes. The effect of ATRX loss in sarcomas is poorly understood, however, and treatments that leverage ATRX deficiency are lacking. Using patient-derived sarcoma cell lines and tumor samples, Dr. Nacev aims to understand epigenetic dysregulation in ATRX-deficient sarcomas, to determine how this affects antitumor immunity, and to identify new therapeutic vulnerabilities.
Institution
University of Pittsburgh
Sponsor(s) / Mentor(s)
Jeremy N. Rich, MD, and Ronald J. Buckanovich, MD, PhD
Cancer type
Sarcoma
Research area
Chromatin Biology
Award Program
Clinical Investigator
Fyza Y. Shaikh, MD, PhD
Project title
"Defining microbiome stability and longitudinal shifts as biomarkers of tumor response to immune checkpoint inhibitors across multiple malignancies"
Immunotherapy has significantly changed how lung cancer and melanoma are treated. Unfortunately, only a small percentage of patients experience long-lasting responses. Gut bacteria have emerged as a potential predictor of how patients will respond to immunotherapy and may even be adjusted to enhance the effect of immunotherapy. Dr. Shaikh aims to identify features of the gut microbiome that correlate with immunotherapy responses. She will focus on both individual bacteria as they change over the course of treatment and the metabolites made by the entire bacterial community in the colon. The goal of this project, since gut bacteria can be modified, is to develop microbiome-based treatments to be used in combination with immunotherapy to improve response rates or overcome immunotherapy resistance for patients.
Institution
The Johns Hopkins University School of Medicine
Sponsor(s) / Mentor(s)
Cynthia L. Sears, MD, and Drew M. Pardoll, MD, PhD
Cancer type
Lung
Skin
Research area
Immunotherapy
Award Program
Clinical Investigator
Santosha A. Vardhana, MD, PhD
Project title
"Overcoming metabolic suppression of anti-tumor immunity in gastric cancer"
Dr. Vardhana [Gordon Family Clinical Investigator] is exploring the hypothesis that gastric cancers create an inhospitable environment for immune T-cells by limiting the availability of essential nutrients needed by T-cells to produce the cytotoxic proteins that, when released, kill cancer cells. There is evidence that T-cells lose the ability to produce cytotoxic proteins within gastric tumors, while gastric tumors take up and sequester amino acids—the building blocks of all proteins, including cytotoxic proteins—such that they cannot be accessed by T-cells within tumors. Understanding and reversing this metabolic sequestration within gastric tumors may be a novel strategy to enhance T-cell immunity within gastric tumors.
Institution
Memorial Sloan Kettering Cancer Center
Sponsor(s) / Mentor(s)
Charles L. Sawyers, MD
Cancer type
Gastric
Research area
Immunotherapy
Award Program
Clinical Investigator
Named Award
Gordon Family Clinical Investigator
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