Other Cancers

Current Projects
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): Glen Raffel, MD, PhD
Cancer Type: Blood, Other Cancer
Research Area: Experimental Therapeutics
Kathryn R. Taylor, PhD

Dr. Taylor is investigating the impact of neural activity on pediatric high-grade glioma (pHGG) invasion. The innate ability of pHGGs to diffusely infiltrate healthy brain tissue is a classical hallmark of the disease, which represents a major contributor to the devastating prognosis. Using optogenetic techniques to stimulate neuronal activity, she will directly and noninvasively test the effect of activity-dependent secreted proteins on tumor cell invasion in human cancer cells and animal models. She plans to confirm the pro-infiltrative effect of candidate proteins on pHGG and subsequently uncover the mechanisms by which they alter the molecular dynamics of the tumor cell. Her hope is to highlight a novel means by which the neural microenvironment drives glioma progression and most importantly identify a new set of therapeutic targets to limit glioma spread.

Project title: "The effect of neuronal activity on pediatric glioma invasion"
Institution: Stanford University
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Michelle L. Monje, MD, PhD
Cancer Type: Other Cancer, Pediatric, Brain
Research Area: Developmental Biology
Christina M. Termini, PhD

Dr. Termini aims to improve the success of hematopoietic stem cell transplants, which are used in the curative treatment of the majority of patients with leukemia or lymphoma. Prior to transplant, patients must undergo radiation therapy to decrease the number of cancerous blood cells. In order for hematopoietic stem cells to effectively repopulate the blood and immune systems of the transplant recipient, the stem cells must reach the bone marrow where they can expand. Her research focuses on how radiation regulates the abundance of molecules called proteoglycans within the bone marrow and how this impacts stem cell repopulation following transplant. Using in vivo transplantation models and super-resolution microscopy techniques, she will visualize and quantify how proteoglycans regulate stem cell interactions with the bone marrow. Her aim is to identify molecular targets that can be used to accelerate patient recovery following transplantation. 

Project title: "Proteoglycan remodeling of the bone marrow niche regulates hematopoietic stem cell regeneration"
Institution: University of California, Los Angeles
Award Program: Fellow
Sponsor(s) / Mentor(s): John P. Chute, MD
Cancer Type: Other Cancer
Research Area: Stem Cell Biology
Victoria E.H. Wang, MD, PhD

Dr. Wang seeks to understand the mechanisms by which tumor cells become resistant to drug therapy and spread to distant organs. She is utilizing functional genomics tools to identify novel pathways modulating these processes in the hope of developing new therapies to augment treatment response in cancer patients. 

Project title: "The role of the c-Met/Hepatocyte growth factor (HGF) pathway in drug resistance and tumor metastasis"
Institution: University of California, San Francisco
Award Program: Fellow
Sponsor(s) / Mentor(s): Frank McCormick, PhD
Cancer Type: Other Cancer, Lung, All Cancers
Research Area: Chemoresistance
Evan J. Worden, PhD

Dr. Worden examines how the decision to “turn on” or “turn off” genes is determined by a highly coordinated series of events that rely on the chemical modification of histone proteins. Misregulation of histone modification can cause a variety of human cancers. Dr. Worden is using structural biology and biophysical approaches to understand how the precise patterning of histone modifications - the “histone code” - is established. He plans to study the regulatory mechanisms that control histone methylation, which is important for the formation of leukemias.

Project title: "The mechanistic basis of crosstalk between histone H2B ubiquitylation and H3K79 methylation"
Institution: The Johns Hopkins University School of Medicine
Award Program: Fellow
Sponsor(s) / Mentor(s): Cynthia Wolberger, PhD
Cancer Type: Other Cancer
Research Area: Biophysics
Heather L. Yeo, MD

The cost of gastrointestinal cancer care in older adults is high, and hospital readmission after major GI cancer surgery can be particularly costly. The Center for Medicare Services (CMS) estimates that around 75% of these readmissions are preventable. For these patients, early warning signs for dehydration, infection, or other complications, if noted earlier, would allow physicians to intervene and prevent readmission. Dr. Yeo, a surgeon, has worked with programmers from Cornell Tech Campus to develop a Mobile Application (iPhone or Android compatible) for patients undergoing abdominal cancer surgery. The app tracks patients’ mobility and prompts patients to input quantitative and qualitative data regarding pain, fluid status and dietary factors in order to allow physicians to intervene earlier as needed. She is currently piloting the app for feasibility and usability, and improving the user interface so that physicians can use the app to monitor and improve patient care. The next step is a prospective randomized study to evaluate the utility of this mobile app in the prevention of readmission, thus enhancing physician-patient interactions, decreasing costs and, most importantly, improving patient care.

Project title: "Use of mobile applications to evaluate post surgical recovery in aging patients with GI cancer"
Institution: Weill Cornell Medicine
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Manish A. Shah, MD, and Deborah Estrin, PhD
Cancer Type: Gastric, Other Cancer, Colorectal, Pancreatic
Research Area: Outcomes Research
Mark W. Zimmerman, PhD

Dr. Zimmerman studies neuroblastoma, a tumor of the peripheral sympathetic nervous system. In high-risk neuroblastoma tumors, which account for 15% of all childhood cancer deaths, the chromatin remodeling gene CHD5 is often deleted and its loss is associated with poor prognosis. The gene expression program regulated by CHD5 has strong tumor suppressive effects and has thus emerged as a very attractive target for potential anti-cancer therapeutics. CHD5 expression is also altered in other cancer types, indicating a potential role in many different adult and pediatric malignancies. His research elucidating the CHD5 pathway in a zebrafish model of neuroblastoma will lead to significant advances in our understanding of how CHD5 functions as a tumor suppressor

Project title: "Elucidating the mechanism of CHD5-mediated tumor suppression in neuroblastoma"
Institution: Dana-Farber Cancer Institute
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): A. Thomas Look, MD
Cancer Type: Other Cancer, Pediatric
Research Area: Chromatin Biology
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