Other Cancers

Current Projects
Nagarajan Nandagopal, PhD

Dr. Nandagopal is focusing on genes in the bHLH family and their role in signal integration to help decide whether cells grow and divide, differentiate, migrate, or even die. bHLH genes are involved in fate choices in stem cells of the brain, intestines, skin, and other tissues. They are also commonly misregulated in cancers, such as neuroblastomas and glioblastomas. By comparing signal integration by bHLH circuits in normal and cancer cells, Dr. Nandagopal aims to discover how errors in fate decisions occur, and how they can be corrected. 

Project title: Signal integration by bHLH circuits to enable cell fate decisions
Institution: Harvard Medical School
Named Award: Philip O’Bryan Montgomery Jr. MD Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Galit Lahav, PhD, and Sean Megason, PhD
Cancer Type: Other Cancer
Research Area: Systems Biology
Fangfei Qu, PhD

Dr. Qu is using Small Cell Lung Cancer (SCLC), a highly metastatic and lethal subtype of lung cancer, as a model to gain a better understanding of brain metastasis. Brain metastases are the most common type of intracranial tumors; they cause morbidity and mortality in a large number of cancer patients worldwide. The lack of preclinical models for brain metastasis has hampered our ability to better understand how primary tumors spread to the brain and grow there. She will first develop in vivo transplant and ex vivo human "mini brain" cancer models to study SCLC metastatic growth in the brain microenvironment. Using these models, she will determine the molecular and cellular mechanisms of metastatic SCLC growth in the brain. This research will suggest new targets for inhibiting growth of SCLC and other cancers at distal metastatic sites in the brain, paving the way for novel treatment approaches for cancer patients.

Project title: "Decoding the molecular and cellular mechanisms underlying the growth of brain metastases"
Institution: Stanford University
Award Program: Fellow
Sponsor(s) / Mentor(s): Julien Sage, PhD
Cancer Type: Other Cancer
Research Area: Cell Biology
Romain L. Riscal, PhD

Dr. Riscal aims to identify and characterize the molecular mechanisms by which a key enzyme involved in cellular metabolism, Fructose-1,6 bisphosphatase (FBP1), suppresses Hepatocellular Carcinoma (HCC) liver cancer initiation and progression. Recent findings comparing HCC tumors and adjacent normal tissues reveal that FBP1 is consistently underexpressed in HCC tumors, functioning as a tumor suppressor in this setting. Since liver cancer is the third most frequent cause of cancer deaths, his goal is to study more precisely how FBP1 opposes liver cancer progression and to help identify novel therapeutic targets for treating patients.

Project title: "Fructose 1,6 bisphosphatase nuclear localization, new function, and implication in Hepatocellular Carcinoma progression"
Institution: University of Pennsylvania, Philadelphia
Award Program: Fellow
Sponsor(s) / Mentor(s): M. Celeste Simon, PhD
Cancer Type: Other Cancer
Research Area: Cell Biology
Jeremy I. Roop, PhD

Dr. Roop seeks to advance HIV vaccine design efforts by studying the unique antibody response of infants infected with HIV. The 36 million people worldwide who are infected with HIV are at an increased risk for many forms of cancer. Infants who acquire HIV from their mothers rapidly develop broadly active antibodies that are capable of neutralizing a wide diversity of global HIV strains. An understanding of the developmental processes involved in eliciting this broad and potent response may reveal clues vital to vaccine design efforts. His research will develop a novel experimental protocol that will allow a detailed characterization of these infant antibodies, as well as reveal insights into the unique developmental processes by which they arise.  

Project title: "Defining virus-host co-evolutionary dynamics that underlie the unusually broad HIV neutralizing antibody response in infants"
Institution: Fred Hutchinson Cancer Research Center
Named Award: Fayez Sarofim Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Julie M. Overbaugh, PhD
Cancer Type: Other Cancer
Research Area: Virology
Benjamin R. Sabari, PhD

Dr. Sabari studies how the three-dimensional architecture of the genome plays a critical role in gene control and is altered in cancer through non-coding mutations. While many well-defined protein-coding mutations have been identified in T cell acute lymphoblastic leukemia (T-ALL), ongoing whole-genome sequencing efforts of patient T-ALL samples are revealing an unexpected level of non-coding mutations within regulatory elements critical for genome architecture. Dr. Sabari is studying how these patient mutations alter the architecture of the genome, lead to alterations in gene control and subsequent development of T-ALL. He will perform comparative analyses of three-dimensional interaction networks in normal, transformed, and genetically engineered cell populations. These studies promise to reveal novel mechanisms of T-ALL initiation and maintenance. 

Project title: "Investigating the role of aberrant genome structuring in T-ALL"
Institution: Whitehead Institute for Biomedical Research
Award Program: Fellow
Sponsor(s) / Mentor(s): Richard A. Young, PhD
Cancer Type: Other Cancer
Research Area: Epigenetics
Jay F. Sarthy, MD, PhD

Dr. Sarthy is developing new easy-to-use and affordable methods for studying DNA packaging and epigenetics (modification of gene expression) in pediatric cancers with a special focus on diffuse midline gliomas and neuroblastoma. These methods may help explain the drivers of pediatric malignancies and allow clinicians to better monitor response to treatment with the goal of developing new drugs that restore the cell’s ability to package DNA correctly.

Project title: Characterization of the epigenomic landscape of diffuse midline gliomas
Institution: Fred Hutchinson Cancer Research Center
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Steven Henikoff, PhD
Cancer Type: Other Cancer, Pediatric, Brain
Research Area: Epigenetics
Harshabad Singh, MBBS

Cancers involving the lower esophagus (esophageal adenocarcinomas) have dramatically increased in number over the last several decades. The reason for rise in this cancer is not completely understood. However, long before these esophageal cancers arise the normal esophageal multilayered squamous lining (or epithelium) is replaced by a single layered columnar epithelium which has features similar to the lining of the intestine and is known as Barrett’s esophagus. Dr. Singh proposes to investigate the origins and factors governing the genesis of Barrett's esophagus and understand its specific vulnerability to progress to cancer. This work will yield insights into disease mechanisms and reveal novel preventive strategies for esophageal adenocarcinomas.

Project title: "Cellular origins of Barrett’s esophagus and its role in development of adenocarcinoma"
Institution: Dana-Farber Cancer Institute
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Ramesh A. Shivdasani, MD, PhD
Cancer Type: Gastric, Other Cancer
Research Area: Epigenetics
Catherine C. Smith, MD

Acute myeloid leukemia (AML) is one of the deadliest blood cancers. Mutations in the FLT3 gene are the most common of all mutations in AML and are associated with poor outcomes in both adult and pediatric patients. Despite the importance of FLT3 mutations in AML, we still do not understand the way in which FLT3 is regulated and the functional impact of novel FLT3 mutations identified in recent large AML sequencing studies. Drugs targeting FLT3 have been successful in achieving remissions in AML patients but are limited by the rapid development of drug resistance, particularly due to reactivation of abnormal cancer signaling through the oncogene RAS.  Dr. Smith proposes studies to better understand how mutations found in AML patients cause dysregulation of FLT3 function and how activation of RAS signaling contributes to drug resistance and AML development. Her goal is to cultivate novel treatment strategies to target FLT3 in patients that will optimize response rates and prevent disease relapse.

Project title: "Defining structure, function and therapeutic impact of oncogenic FLT3 mutations"
Institution: University of California, San Francisco
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Neil P. Shah, MD, PhD
Cancer Type: Other Cancer
Research Area: Signal Transduction
Melody Smith, MD

Bone marrow transplant (BMT) is a treatment approach where cells from a healthy donor are given to a patient with blood cancer who has not responded to other treatments. Unfortunately, there are risks to this procedure such as graft-versus-host disease (GVHD), which occurs if the cells from the donor attack the "foreign" patient tissue; this can cause serious organ damage and is life-threatening. Melody is investigating an approach to decrease GVHD while also maintaining the benefits of BMT, specifically graft versus tumor (GVT). She utilizes T immune cells from the donor and enables them to express a B cell marker, CD19; these cells can induce complete remissions in patients with CD19-positive leukemia and lymphoma. Administration of these cells following BMT mediates persistent GVT and decreased GVHD. Given that donor T cells are the culprits that cause GVHD, the finding of decreased GVHD in her model was paradoxical. She will now translate these pre-clinical findings to a clinical trial in order to benefit patients.

Project title: "CD19 targeted donor T cells improve graft versus tumor activity and reduce graft versus host disease"
Institution: Memorial Sloan Kettering Cancer Center
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Marcel R.M. van den Brink, MD, PhD
Cancer Type: Blood, Other Cancer
Research Area: Immunotherapy
Sakiko Suzuki, MD

Despite many recent advances, today’s treatment of leukemia still relies on medications that have very toxic side effects and can cause death. Therefore, it is crucial to search for new types of therapies that directly target leukemia without harming the normal cells of the body. A gene called MPL encodes a protein found to be important for the growth and survival of a significant proportion of Acute Myeloid Leukemias (AMLs) and other blood diseases including Essential Thrombocythemia (ET), a malignancy affecting the platelet-producing cells of the bone marrow. Sakiko has been focusing on the function of a truncated variant of MPL produced by splicing out a section of the MPL RNA message used to make the protein. This variant, MPL-TR, opposes the function of MPL in cells; she believes that increasing MPL-TR in leukemia cells will suppress their growth. Anti-sense oligonucleotides (AONs) are very short segments of RNA or DNA that can be constructed to bind specifically to RNA messages in the cell, so no other genes are affected. By targeting AONs to the regions in MPL RNA important for splicing, she proposes that leukemia cells will make more MPL-TR, thus inhibiting their growth and survival. She will test a series of AONs targeting human MPL splicing, designed to enhance levels of MPL-TR. These experiments will provide the foundation for establishing a clinical trial with the novel, targeted AON. The principles founded by this project would also be broadly applicable for targeting splicing in other genes essential for multiple forms of leukemia and lymphoma.

Project title: "AON-directed alternative splicing as a novel therapy for leukemia"
Institution: University of Massachusetts Medical School
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Michelle A. Kelliher, PhD, and Peter E. Newburger, MD
Cancer Type: Blood, Other Cancer
Research Area: Experimental Therapeutics
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