Other Cancers

Current Projects
Lauren E. Cote, PhD

Dr. Cote is exploring embryonic development to better understand how cells cooperate and build complex tissues. Since cancer cells often erroneously redeploy developmental programs and behaviors, her research into how neighboring cells align will yield insights into how cancerous cells metastasize and invade other tissues. Dr. Cote is combining tissue-specific genetic manipulations and laser cell ablations with live imaging during Caenorhabditis elegans digestive tract development to reveal how intracellular organization in one cell type can influence the alignment, polarity, and function of cells in the neighboring tissues.

Project title: "Constructing one continuous digestive tract, cell by cell"
Institution: Stanford University
Award Program: Fellow
Sponsor(s) / Mentor(s): Jessica L. Feldman, PhD
Cancer Type: Gastric, Other Cancer, Breast, Colorectal, All Cancers
Research Area: Developmental Biology
Allison L. Didychuk, PhD

Kaposi's sarcoma herpesvirus (KSHV) is a human oncogenic virus and the causative agent of cancers including Kaposi’s sarcoma, primary effusion lymphoma, and Multicentric Castleman disease. The related human herpesvirus Epstein-Barr Virus (EBV) is even more prevalent than KSHV, and is linked to cancers including Burkitt’s lymphoma, Hodgkin’s lymphoma, and nasopharyngeal carcinoma. Dr. Didychuk [The Rhee Family Breakthrough Scientist] is investigating the mechanisms by which KSHV co-opts the cellular host machinery to produce its own gene products in a manner distinct from other viruses and host cells. A molecular understanding of how herpesviruses hijack the late gene transcription machinery will reveal new therapeutic weaknesses in the viral lifecycle and allow for structure-guided design of novel anti-viral drug targets.

Project title: “Viral mimics of host transcription factors in oncogenic herpesviruses”
Institution: Yale University
Named Award: The Rhee Family Breakthrough Scientist
Award Program: Dale Frey Scientist
Cancer Type: Blood, Other Cancer, Sarcoma
Research Area: Virology
Jonathan C. Dudley, MD

Earlier cancer detection usually means a greater chance of remission or cure, but cost-effective and highly specific cancer screening is not yet available for most cancers. More than 90 percent of cancers harbor aneuploidy, an abnormal number of chromosomes in a cell; this abnormality is highly specific for cancer and can be detected with DNA sequencing. Dr. Dudley [Gordon Family Physician-Scientist] is developing a new approach for detecting cells with abnormal amounts of DNA, which could identify cancer sooner. He aims to apply this approach to urine and Pap smear samples to create an inexpensive and sensitive screening test for bladder, ovarian and endometrial cancers.

Project title: "Earlier detection of cancer in body cavity fluids through aneuploidy analysis after cell enrichment and partitioning"
Institution: The Johns Hopkins University School of Medicine
Named Award: Gordon Family Physician-Scientist
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Bert Vogelstein, MD
Cancer Type: Gynecological, Kidney and Bladder
Research Area: Diagnostics
Kiara C. Eldred, PhD

Dr. Eldred is focusing on retinoblastoma, a tumor of the eye that primarily occurs in children. She is developing three-dimensional tissue cultures that replicate the complexity of the human retina. Using these retinal “organoid” models, Dr. Eldred will generate mutations of the retinoblastoma (RB1) gene in previously healthy tissue to observe the effects of different mutations on the formation and growth of retinoblastoma. She hopes this will also shed light on the roles of tumor-causing oncogenes and tumor suppressors involved in retinoblastoma progression. A deeper understanding of specific RB1 mutations may guide the prevention, diagnosis, and development of individualized treatment plans for patients with retinoblastoma and other cancers involving mutations in the RB1 pathway.   

Project title: "Dissecting the mechanisms of tumorigenesis in the human retina"
Institution: University of Washington
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Thomas Reh, PhD
Cancer Type: Other Cancer, Pediatric, All Cancers
Research Area: Cell Biology
Catherine A. Freije, PhD

Dr. Freije [Berger Foundation Fellow] is studying how the genetic diversity of hepatitis B virus (HBV) is shaped by its need to replicate and interact with specific host genes. Current antiviral therapeutics for HBV merely suppress infection and do not cure disease; as a result, patients with chronic HBV infection are at risk of developing liver cancer. Dr. Freije plans to uncover essential genomic regions that HBV needs to survive and persist, as well as those that counteract host genes that function to restrict these activities. This approach could provide insight into the progression of disease and has the potential to identify new antiviral therapeutics and ultimately reduce the incidence of HBV-associated liver cancer.

Project title: "Investigating the role of fitness and host pressure in shaping hepatitis B diversity"
Institution: The Rockefeller University
Named Award: Berger Foundation Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Charles M. Rice, PhD
Cancer Type: Other Cancer
Research Area: Virology
Jennifer M. Kalish, MD, PhD

Dr. Kalish is studying a rare hereditary syndrome called Beckwith-Wiedemann syndrome (BWS), which increases the risk of children developing kidney and liver cancers. These individuals have epigenetic changes on chromosome 11 that are found in other types of cancers. Epigenetic markers modify DNA so gene expression is turned on or off; changes in this process can cause cancer. By understanding how cancer is triggered in BWS, Dr. Kalish aims to identify pathways that can be targeted for the development of new treatments both for BWS patients and for others with cancers that have similar epigenetic changes. As a physician-scientist, Dr. Kalish established the BWS Registry, which compiles both clinical data and patient samples, and created the first human cell-based models of BWS.

Project title: "Epigenetic and genetic mechanisms of cancer in Beckwith-Wiedemann Syndrome"
Institution: Children's Hospital of Philadelphia
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Marisa S. Bartolomei, PhD, and Garrett M. Brodeur, MD
Cancer Type: Kidney and Bladder, Other Cancer, Pediatric
Research Area: Epigenetics
Aaron E. Lin, PhD

Dr. Lin [Walter Isaacson Fellow] is studying how hepatitis C virus (HCV) rewires cell biology and causes liver cancer. Modern HCV antiviral therapies are effective in curing hepatitis, but puzzlingly, recovered patients sometimes still develop cancer. This suggests that infection and subsequent inflammation permanently alter liver cells, but how this leads to cancer remains unclear. Dr. Lin is developing a CRISPR-based molecular "recorder" to determine whether cells that become more cancer-like have a history of infection and inflammation. This technology could identify genes that predispose healthy liver cells to infection, chronic immune stimulation, and transformation to cancer cells, which could point to potential therapeutic targets to interrupt the development of liver and other cancers.

Project title: "Contact tracing within an organism: developing a genome editing platform to record the history of virus-infected and transformed cells"
Institution: Princeton University
Named Award: Walter Isaacson Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Alexander Ploss, PhD, and Brittany Adamson, PhD
Cancer Type: Other Cancer
Research Area: Virology
David G. McFadden, MD, PhD

Mitochondria, the “power plants” of the cell, carry their own DNA that encodes proteins important to producing the energy necessary to run a normal cell. Most cancers also depend on mitochondria to promote the growth and division of tumor cells. Dr. McFadden has shown that a form of thyroid cancer called Hürthle cell carcinoma carries mutations in the mitochondrial DNA, which are maintained in primary tumors and metastases resected from the same patients. He will study energy metabolism in Hürthle cell cancers by feeding the tumors isotope forms of nutrients (tracers) that are used to produce energy and support cell growth. The tracers can be visualized to reveal how metabolism is re-wired in these tumors and to identify novel ways to target altered mitochondrial metabolism in cancers with such genetic mutations. 

Project title: "Identifying metabolic vulnerabilities in Hürthle cell carcinoma"
Institution: University of Texas Southwestern Medical Center
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Steven L. McKnight, PhD, and Ralph J. DeBerardinis, MD, PhD
Cancer Type: Other Cancer
Research Area: Biochemistry
Vitor Mori, PhD

New technologies developed in the last decade have enabled chemotherapy to be delivered directly to lung tumors intratumorally in contrast to systemic delivery that affects the whole body. Recent studies have shown a partial or complete response ratio of 71% with significantly fewer side effects for patients treated intratumorally with cisplatin. Dr. Mori is modeling cisplatin pharmacodynamics following injections, taking into consideration the heterogeneity of the tumor microenvironment. This research aims to optimize drug delivery strategy to enhance targeting tumor cells while reducing side effects. 

Using segmented high-resolution CT images, Dr. Mori assigns a set of features to each voxel of the tumor (diffusivity, clearance rate, and intracellular threshold concentration needed to induce cell apoptosis). He then simulates the competing physical mechanisms inside the tumor to assess the total tumor volume with an intracellular concentration above the threshold to estimate the minimal required dose based on the tumor morphology and the number of injections. The model is implemented using MatLab.

Project title: "EBUS-TBNI of cisplatin optimization in heterogeneous lung tumors"
Institution: University of Vermont
Award Program: Quantitative Biology Fellow
Sponsor(s) / Mentor(s): Jason H.T. Bates, PhD, DSc, and C. Matthew Kinsey, MD
Cancer Type: Kidney and Bladder, Lung
Research Area: Biomedical Engineering
Nagarajan Nandagopal, PhD

Dr. Nandagopal [Philip O’Bryan Montgomery Jr. MD Fellow] is focusing on genes in the bHLH family and their role in signal integration to help decide whether cells grow and divide, differentiate, migrate, or even die. bHLH genes are involved in fate choices in stem cells of the brain, intestines, skin, and other tissues. They are also commonly misregulated in cancers, such as neuroblastomas and glioblastomas. By comparing signal integration by bHLH circuits in normal and cancer cells, Dr. Nandagopal aims to discover how errors in fate decisions occur, and how they can be corrected. 

Project title: "Signal integration by bHLH circuits to enable cell fate decisions"
Institution: Harvard Medical School
Named Award: Philip O’Bryan Montgomery Jr. MD Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Galit Lahav, PhD, and Sean G. Megason, PhD
Cancer Type: Other Cancer, Brain
Research Area: Systems Biology
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