Other Cancers

Current Projects
Alexandra Nguyen, PhD

Dr. Nguyen aims to identify the molecular differences between cancer cells and healthy cells, using large-scale genetic approaches in acute myeloid leukemias. Cancer cells exhibit a high degree of diversity in the cellular pathways utilized for survival. Identifying these cellular differences could provide a method to strategically target and kill cancerous cells while minimizing the off-target effects to healthy cells.

Project title: "Defining the cell type specific cell division requirements in acute myeloid leukemias"
Institution: Whitehead Institute for Biomedical Research
Award Program: Fellow
Sponsor(s) / Mentor(s): Iain M. Cheeseman, PhD
Cancer Type: Blood, Other Cancer
Research Area: Cancer Genetics
Juhee Pae, PhD

Dr. Pae is investigating the regulation of immune B cell proliferation in Germinal Centers (GCs). While this process is critical for bodies to resist infection, it must be carefully regulated. On one hand, not having enough B cells can lead to immunodeficiency and susceptibility to infections. Conversely, inappropriate activation is a major driver of malignant transformation and cancers such as B cell lymphomas. Dr. Pae’s research has the potential to shed light on how lymphomas form and to aid in the rational design of cancer therapeutics.

Project title: "Mechanisms of germinal center B Cell proliferation"
Institution: The Rockefeller University
Named Award: Berger Foundation Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Gabriel D. Victora, PhD
Cancer Type: Blood, Other Cancer
Research Area: Basic Immunology
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
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: Blood, 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
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
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