Other Cancers

Current Projects
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
Named Award: William Raveis Charitable Fund Physician-Scientist
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Ramesh A. Shivdasani, MD, PhD
Cancer Type: Gastric, Other Cancer
Research Area: Epigenetics
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

Myelodysplastic syndromes (MDS) are a heterogeneous group of blood disorders characterized by abnormal maturation of the hematopoietic blood cells and premature death of these immature cells leading ultimately to bone marrow failure. Patients with MDS are also at increased risk of developing acute myelogenous and acute lymphoblastic leukemias. Currently available treatments for MDS include serial blood transfusions for refractory anemia, hematopoietic cell growth hormone therapy, and eventually chemotherapy and bone marrow transplantation. However, bone marrow transplants are not an option for some patients due to lack of a matched donor. Additionally, not all patients are eligible for this treatment because of significant risks for long-lasting and severe side effects. New effective treatments are therefore needed.

Mutations in mRNA splicing factors, including SF3B1 and SRSF2, are the most common genetic alterations found in MDS patients. MDS is associated with an inflammatory gene signature suggesting that chronic inflammation contributes to disease pathogenesis. Dr. Suzuki will test whether these mutations sensitize blood cells to necroptosis, an inflammatory form of cell death, resulting in systemic inflammation that contributes to MDS disease propagation. She will also ask whether inhibiting necroptosis can rescue cells with SF3B1 or SRSF2 mutations and allow them to mature normally. If she proves that necroptosis plays a significant role in MDS disease, her work could then be rapidly translated to benefit MDS patients by using necroptosis inhibitor therapies that are currently being tested in the clinic for other diseases. These studies could lead to novel therapeutic options for MDS patients.

Project title: "Inflammatory cell death pathways in Myelodysplastic Syndromes"
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
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: Blood, Other Cancer
Research Area: Stem Cell Biology
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 L. Estrin, PhD
Cancer Type: Gastric, Other Cancer, Colorectal, Pancreatic
Research Area: Outcomes Research
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