All Cancers

Current Projects
Bryan C. King, PhD

Dr. King (Berger Foundation Fellow) is studying mechanisms by which nutrient-deprived cancer cells utilize extracellular proteins as a source of amino acids to promote their growth and survival. The bulk uptake of extracellular material, through a process called macropinocytosis, is a major means of nutrient uptake in single-celled, amoeboid organisms. Recent evidence suggests that mutations prevalent in cancer cells can activate this ancient scavenging mechanism. He will investigate how signaling pathways that respond to changes in nutrient availability, such as the AMP-activated protein kinase (AMPK), can influence this process. Since many agents currently used in the clinic act by cutting off the supply of nutrients to the tumor, these studies may give insights into how cancer cells develop resistance to therapy.

Project title: "AMPK-induced catabolism of extracellular proteins: a novel survival mechanism for nutrient-deprived cancer cells"
Institution: Memorial Sloan Kettering Cancer Center
Named Award: Berger Foundation Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Craig B. Thompson, MD
Cancer Type: All Cancers
Research Area: Cell Biology
Ralph E. Kleiner, PhD

Many cancers result from an alteration in a cell's genetic material or DNA -- the basic instruction manual for life. Even a subtle change in DNA sequence can cause dramatic effects and reprogram normal cells, leading to cancer. While many cancers have genetic components, a more recent paradigm in cancer biology has been the study of cellular reprogramming founded in epigenetic or epitranscriptomic changes, which occur without alteration of the underlying DNA sequence. Dr. Kleiner is integrating chemistry and biology approaches to investigate alterations in the chemical composition of RNA, and to understand how these changes are involved in the cellular reprogramming linked to cancer. Changes in RNA chemistry can result in profound effects on cells, as RNA serves as the intermediate between the information encoded in DNA and proteins, the cell's functional effector molecules. He is also interested in understanding how RNA interacts with known anti-cancer drugs including 5-FU and cisplatin. He aims to shed light on the fundamental cellular mechanisms involved in the development of cancer and to provide new opportunities to therapeutically target cancer.

Project title: "Using chemistry to illuminate DNA and RNA damage processes in cells"
Institution: Princeton University
Award Program: Dale Frey Scientist
Cancer Type: All Cancers
Research Area: Chemical Biology
Brian J. Laidlaw, PhD

Dr. Laidlaw is investigating the mechanisms underlying immune cell positioning following viral infection and tumor challenge. Localization of immune cells to particular sites within the tissue is critical for their maintenance and protective capacity upon reencountering an antigen. How immune cell migration within the tissue is regulated remains poorly understood. His studies should significantly enhance our understanding of immune cell trafficking and inform the development of new immunotherapies against cancer that modulate these pathways to promote tumor regression.

Project title: "Role of EBI2 in the regulation of lymphocyte migration during viral infection and cancer"
Institution: University of California, San Francisco
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Jason Cyster, PhD
Cancer Type: All Cancers
Research Area: Basic Immunology
Christopher P. Lapointe, PhD

Dr. Lapointe examines how the synthesis of proteins (translation) is controlled, as dysregulated translation is a ubiquitous feature of cancer. He is focused on a key challenge: how regulation that originates at the “tail” end of a messenger RNA (mRNA, a genetic molecule that encodes a protein) impacts the start of translation, which occurs near the beginning of the mRNA. His goal is to reveal and analyze dynamic pathways that underlie this fundamental mechanism to control gene expression. Using an integrated approach of single-molecule fluorescence microscopy, structural, and biochemical strategies, this research should yield important insights into how translation is precisely regulated and how it is disrupted in a wide array of cancers. 

Project title: "Regulatory roles of the 3' untranslated region in human translation"
Institution: Stanford University School of Medicine
Award Program: Fellow
Sponsor(s) / Mentor(s): Joseph Puglisi, PhD
Cancer Type: All Cancers
Research Area: Biophysics
Tera C. Levin, PhD

Dr. Levin [HHMI Fellow] studies how resident microorganisms can manipulate the development of their animal hosts. Through novel genetic approaches, she will explore the mechanisms used by the bacterium Legionella to dramatically disrupt the cell divisions of its host, amoeba. Because cancerous growth is often driven by the dysregulation of developmental signaling pathways, understanding the mechanistic impacts of resident microbes promises to illuminate both normal and cancer development.

Project title: "Master microbial manipulators: how hosts are shaped by bacterial infections"
Institution: Fred Hutchinson Cancer Research Center
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Harmit S. Malik, PhD
Cancer Type: All Cancers
Research Area: Basic Genetics
Evan C. Lien, PhD

Dr. Lien is studying how diet and nutrition impact cancer cell metabolism and tumor progression. The way cancer cells utilize nutrients to support their growth and proliferation is determined not only by cancer-promoting genetic alterations, but also by the tumor’s interactions with its local environment. Diet-mediated changes in whole-body metabolism and nutrient availability are an important part of a tumor’s metabolic environment, and a better understanding of how diet modulates nutrient availability and utilization by cancer cells is needed. Moreover, the question of whether certain diets may improve prognosis is of great importance to cancer patients. He aims to provide insight into which cancer types respond to various diets, how diet impacts cancer cell metabolism to mediate these responses, and whether dietary interventions may open new therapeutic opportunities in combination with current cancer treatments. 

Project title: "Impact of diet on tumor metabolism and progression"
Institution: Koch Institute for Biomedical Research
Award Program: Fellow
Sponsor(s) / Mentor(s): Matthew G. Vander Heiden, MD, PhD
Cancer Type: All Cancers
Research Area: Biochemistry
Lucy Liu, PhD

Dr. Liu studies cachexia, a complex metabolic syndrome characterized by a rapid and irreversible loss of body mass, which significantly impedes disease treatment success. This body-wasting phenomenon is a common feature in many types of cancers, but the causes are unknown. She is investigating the tumor-derived signaling mechanisms that lead to systemic cachexia and muscle wasting. As no current therapies exist for the reversal or delay of cachexic symptoms, identifying the triggers that lead to systemic body mass loss is imperative to improve our understanding of all cancers and to identify putative drug targets.

Project title: "In vivo characterization of muscle autophagy in health and disease"
Institution: Harvard Medical School
Award Program: Fellow
Sponsor(s) / Mentor(s): Norbert Perrimon, PhD
Cancer Type: All Cancers
Research Area: Cancer Genetics
Kai Mao, PhD

Dr. Mao is studying the cell’s cytoskeleton, which provides the physical structure and shape of a cell. The cytoskeleton is an attractive target for cancer chemotherapy because of its central function in mitosis or cell division, but these chemotherapeutic agents have very high toxicity. He hypothesizes that the next generation of chemotherapy will benefit from the inhibition of these toxin response pathways. He will examine how cells respond to such drugs, with the goal of applying these findings to attenuate the drugs’ side effects.

Project title: "Mechanisms of xenobiotic surveillance and regulation"
Institution: Massachusetts General Hospital
Award Program: Fellow
Sponsor(s) / Mentor(s): Gary Ruvkun, PhD
Cancer Type: All Cancers
Research Area: Toxicology/Toxicogenomics
Timothy D. Martin, PhD

Dr. Martin [Marion Abbe Fellow] focuses on genomic instability, a hallmark of virtually all cancers that underlies the mutations and aneuploidy (incorrect chromosome number) changes that perturb oncogenes and tumor suppressor genes (TSGs). Patient tumor sequencing has unveiled common genomic alterations across different cancers. Recent work described how the cancer genome is shaped by the loss of many genes and gene clusters. Despite the high frequency of TSG mutations and recurrent multi-gene focal deletions in cancer, the relative contribution of TSGs and focal deletions to tumor growth has not yet been compared. The goal of this project is to precisely recreate these genomic alterations and directly test how each contributes to oncogenesis.

Project title: "Investigating the role of aneuploidy and haploinsufficiency in driving tumorigenesis"
Institution: Brigham and Women's Hospital
Named Award: Marion Abbe Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Stephen J. Elledge, PhD
Cancer Type: Breast, Colorectal, All Cancers
Research Area: Cancer Genetics
Benjamin L. Martin, PhD

Hallmarks of cancer progression are increases in both uncontrolled proliferation and invasive behavior, leading to the spread of tumor cells throughout the body. This collaborative project is founded upon an experimental observation made by Dr. Matus, in the model roundworm, C. elegans, that cell invasion and cell division are mutually exclusive behaviors. In other words, a cell cannot simultaneously invade and divide. This functional link between cell cycle arrest and invasive behavior has not been directly made before, although in a variety of cancers there is correlative data suggesting that tumor cells become less proliferative during invasion. Cell invasive behavior occurs during normal embryonic development, immune surveillance, and is dysregulated during metastatic cancer progression. As two cell and developmental biologists, Dr. Matus and Dr. Martin, will leverage their expertise in the strengths of two model systems, C. elegans and the zebrafish, D. rerio, to identify how regulation of the cell cycle intersects with acquisition of cell invasive behavior. Together, they will examine and manipulate the cell cycle state of human cancer cells during metastasis, visualizing invasive behavior at high resolution using light sheet microscopy. Insights from their work will have profound implications in future design of therapeutics to eradicate invasive cells that may escape traditional chemotherapeutic agents that only target actively dividing cells.

Project title: "Cell cycle regulation of cellular behaviors associated with cancer metastasis"
Institution: Stony Brook University
Award Program: Innovator
Cancer Type: All Cancers
Research Area: Proliferation/Cell Cycle
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