All Cancers

Current Projects
J. Scott P. McCain, PhD

Many organisms (including humans) have evolved circadian rhythms to adapt to the rising and setting of the sun, and recent discoveries point to circadian rhythms even in non-photosynthetic bacteria. Bacteria have a huge impact on human health, including cancer risk and treatment outcomes, and yet we may be missing a fundamental aspect of their nature. Dr. McCain is studying circadian rhythms in bacteria: how, why, and who? He is using modern genomics and classic genetics approaches to dissect how bacteria can “predict” their environment from day to day. He is also examining why bacteria do this—what are the costs and benefits of a circadian rhythm? Finally, he is looking broadly across bacteria to examine the prevalence of circadian rhythms. This project will provide fundamental insights into the biology of bacteria and circadian rhythms, both of which have direct implications for cancer biology. Dr. McCain received his MSc and PhD from Dalhousie University and his BSc from the University of Western Ontario.

Project title: "Circadian clocks in non-photosynthetic bacteria: mechanisms and impacts"
Institution: Massachusetts Institute of Technology
Award Program: Fellow
Sponsor(s) / Mentor(s): Gene-Wei Li, PhD
Cancer Type: All Cancers
Research Area: Microbiology
Conor J. McClune, PhD

Dr. McClune [HHMI Fellow] investigates plant biosynthesis of therapeutic compounds. Approximately half of FDA-approved chemotherapeutics, including first line drugs like paclitaxel (Taxol) and vinblastine (Velban), derive from the arsenal of defensive chemicals that plants synthesize. Unfortunately, both the discovery of new plant-derived therapies and their scalable production are limited by intrinsic challenges of plant biology and genomics. Dr. McClune is developing systematic methods for identifying the biosynthetic pathways plants use to produce defensive molecules. Using single-cell technology, he will characterize rare cells responsible for synthesizing potentially beneficial chemicals and identify the enzymes they use to produce such molecules.

Project title: "Resolving plant biosynthesis of therapeutic compounds by systematic perturbation, measurement, and metabolic phenotyping at single-cell scale"
Institution: Stanford University
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Elizabeth S. Sattely, PhD, and Polly M. Fordyce, PhD
Cancer Type: All Cancers
Research Area: Biochemistry
Jon McGinn, PhD

Dr. McGinn studies how bacterial pathogens sense and manipulate their human hosts. Dr. McGinn is focusing on the tick-borne bacterial pathogen Rickettsia parkeri, which can only survive within eukaryotic host cells. By uncovering novel interactions between host and pathogen, his work may reveal new insights into how human cells work and what goes awry in disease states. He is also developing tools to manipulate key virulence pathways in Rickettsia parkeri that can be used to transform the bacteria into a vehicle for delivering antigens or new drugs directly to cancer cells.

Project title: "Dissecting the genetic networks underlying host subversion during Rickettsia infection"
Institution: Massachusetts Institute of Technology
Award Program: Fellow
Sponsor(s) / Mentor(s): Rebecca Lamason, PhD
Cancer Type: All Cancers
Research Area: Microbiology
Kara L. McKinley, PhD

Dr. McKinley studies the lining of the uterus called the endometrium. The human endometrium is a uniquely powerful system to understand fundamental principles of regeneration, as it regenerates after menstruation approximately 400 times over the reproductive lifespan. Understanding this remarkable regenerative event is critical to combat the growing incidence of endometrial cancers, and to address the longstanding unmet needs of patients with endometriosis and adenomyosis. The McKinley laboratory studies the cellular and molecular mechanisms of endometrial regeneration, with a view to improving endometrial cancer screening and developing new fertility-preserving treatments.

Project title: "Physiology and pathology of the uterus"
Institution: Harvard University
Award Program: Dale Frey Scientist
Cancer Type: Gynecological, All Cancers
Research Area: Cell Biology
Colleen N. McLaughlin, PhD

Dr. McLaughlin [HHMI Fellow] is using the developing nervous system to study metastasis, the primary cause of cancer-related fatalities. In metastasis, cell surface and secreted molecules enable cells to travel through diverse environments and invade distant tissues. Likewise, growing axons in the developing nervous system use similar sets of cell surface proteins to traverse long distances to form precise connections with their synaptic partner cells. Dr. McLaughlin aims to define the mechanisms used by cell surface proteins to promote axon targeting, which will provide critical insight into how these molecules are harnessed by malignant cells during metastasis. 

Project title: "Cell surface mechanisms of neural circuit assembly"
Institution: Stanford University
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Liqun Luo, PhD
Cancer Type: All Cancers
Research Area: Neuroscience
Rebecca S. Moore, PhD

Sleep problems may be a risk factor for developing certain types of cancer—lung, colon, pancreas, and breast—and may affect the progression of these cancers and the effectiveness of their treatment. Conversely, symptoms of cancer or side effects of treatment, including restless legs and obstructive sleep apnea, may cause sleeping problems, reducing quality of life. Understanding the complex relationship between cancer and sleep creates opportunities to improve health, treatment options, and quality of life. Specifically, understanding how the peripheral nervous system and the brain regulate both the timing and rhythmicity of sleep (i.e., circadian control), and the balance between time awake and growing sleep pressure (i.e., homeostatic control), could improve survival rates and the quality of cancer treatment. To this end, Dr. Moore [HHMI Fellow] aims to identify the role of circulating dietary cholesterol on sleep and to conduct a targeted genetic screen to identify peripherally secreted proteins that affect either the circadian or the homeostatic control of sleep. These results will provide a means for therapeutic interventions to ameliorate the effects of sleep disruption. Dr. Moore received her PhD from Princeton University and her MS and BS from the City College of New York.

Project title: "Investigation of the role of peripheral secreted molecules on sleep and circadian rhythms"
Institution: University of Pennsylvania
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Amita Sehgal, PhD
Cancer Type: All Cancers
Research Area: Basic Genetics
Stefan Niekamp, PhD

Dr. Niekamp [Dennis and Marsha Dammerman Fellow] studies how gene expression programs are regulated in normal and cancer cells. The ability to switch specific genes "on" and "off" is partly encoded by multiprotein complexes competing for access to target DNA sequences in chromatin structures. The relative distribution of these activating or repressive complexes along chromatin regulates gene expression, and a shift in the balance of these complexes is a hallmark of many cancers. Dr. Niekamp aims to determine how chromatin accessibility is achieved by the competition between activating and repressive complexes, and to understand how well-known cancer mutations disrupt the fine-tuned balance.

Project title: "Understanding the switch: Competition between chromatin remodeler and polycomb repressive complexes"
Institution: Massachusetts General Hospital
Named Award: Dennis and Marsha Dammerman Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Robert E. Kingston, PhD
Cancer Type: All Cancers
Research Area: Biophysics
Christopher Noetzel, PhD

As different tissues in the body form, cells need to undergo a complex, precisely timed series of differentiation programs to form specialized cell types. Importantly, premature or delayed initiation of these programs can contribute to cancer formation. However, how timing of cellular differentiation is encoded on a molecular level is poorly understood. Dr. Noetzel is using the protozoan parasite Cryptosporidium parvum as a simplified model of eukaryotic differentiation. After infecting the intestinal lining of a mammalian host, these single-celled parasites undergo exactly three rounds of asexual replication before collectively differentiating into gametes. These studies will investigate how this hard-wired, intrinsic developmental timer is encoded. In his project, Dr. Noetzel aims to understand how these parasites "count to three," which will inform our basic understanding of how eukaryotic cells keep track of time during development. Dr. Noetzel received his PhD from the Weill Cornell Medical College, Cornell University, New York and his MSc and BSc from Georg-August-University, Göttingen.

 

Project title: "How do eukaryotic cells count cell cycles? Intrinsic regulation of quantized asexual replication cycles and commitment to sexual differentiation in the protozoan parasite Cryptosporidium parvum"
Institution: University of Pennsylvania
Award Program: Fellow
Sponsor(s) / Mentor(s): Boris Striepen, PhD
Cancer Type: All Cancers
Research Area: Microbiology
Katy Ong, PhD

Dr. Ong [The Mark Foundation for Cancer Research Fellow] is investigating the molecular basis of paraneoplastic syndromes, which occur when a cancer causes unusual symptoms due to hormones produced by the tumor or antibodies produced by the immune system. They can affect the function of various distant tissues and organs in cancer patients, with deadly consequences. Dr. Ong is utilizing a new genetic tumor model in Drosophila that simulates many human paraneoplastic disorders: cachexia, immune dysfunction and early lethality. She aims to uncover how tumor cells impose physiological changes in host tissues at a distance with the hope of uncovering footholds for novel treatments.

Project title: "Long-range tumor-host signaling mechanisms driving paraneoplastic syndromes"
Institution: University of California, Berkeley
Named Award: The Mark Foundation for Cancer Research Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): David Bilder, PhD
Cancer Type: All Cancers
Research Area: Cell Biology
Tristan Wold Owens, PhD

Dr. Owens [Suzanne and Bob Wright Fellow] focuses on heat shock proteins (HSPs) and their “master regulator” called heat shock transcription factor 1 (HSF1). The transformation and growth of cancers causes a wide array of cellular stresses including metabolic changes, genomic instability, and protein misfolding that would halt the growth of a normal cell. Tumor cells, however, depend on cellular stress response machinery, like HSPs, for their survival. HSF1 is critical to tumor development and progression, and HSF1 activity is strongly correlated with poor prognosis in many common cancers. For decades, efforts to develop cancer therapies targeting HSPs have failed. Dr. Owens aims to understand how HSPs and HSF1 interact to regulate activity, and how this regulation is co-opted to promote tumor growth and progression.

Project title: "Molecular mechanisms of heat shock transcription factor 1 in cancer"
Institution: University of California, San Francisco
Named Award: Suzanne and Bob Wright Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): David A. Agard, PhD
Cancer Type: Other Cancer, Breast, Prostate, All Cancers
Research Area: Biochemistry
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