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.

Dr. Didychuk is investigating the mechanism by which the Kaposi’s sarcoma herpesvirus (KSHV) co-opts the cellular host machinery to produce its own gene products in a manner distinct from other viruses and host cells. This research should reveal insights into this unique mode of transcriptional control. KHSV is an oncogenic virus that causes various cancers including, Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease, in immunocompromised individuals.

One of the unique features of liver cancer is the way in which it obtains and uses different forms of energy, especially fats. Drs. Evason and Ducker found that a certain type of fat (phosphatidylcholine lipids) is elevated in both zebrafish and human liver cancer cells. They are using zebrafish, which form tumors similar to the human disease and can be easily manipulated to study liver cancer. The goal of this project is to determine why phosphatidylcholine lipid levels are higher in liver cancer and how they might be targeted with drugs to prevent or cure this disease.

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 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.

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.   

One of the unique features of liver cancer is the way in which it obtains and uses different forms of energy, especially fats. Drs. Evason and Ducker found that a certain type of fat (phosphatidylcholine lipids) is elevated in both zebrafish and human liver cancer cells. They are using zebrafish, which form tumors similar to the human disease and can be easily manipulated to study liver cancer. The goal of this project is to determine why phosphatidylcholine lipid levels are higher in liver cancer and how they might be targeted with drugs to prevent or cure this disease.

Dr. Freije 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.

Christopher’s research centers on the earliest steps whereby normal cells transform into abnormal cells with the potential to become cancer. He will focus on better understanding the first steps of the process by which normal blood cells become lymphomas, cancers that are generally thought to arise from blood cells that have already committed to becoming lymphocytes, an important component of the immune system. He hypothesizes, however, that some lymphomas actually arise from earlier hematopoietic stem cells (HSCs). He will interrogate this hypothesis by studying a cohort of lymphoma patients who also have detectable genetic mutations in HSCs that are known to be associated with blood cancers – a condition known as clonal hematopoiesis of indeterminate potential, or CHIP – to determine whether the mutations in the HSCs were the earliest events in the development of the patients’ lymphomas. Having a better understanding of lymphomas’ cellular basis will hopefully allow new insights into their clinical behavior and therapeutic vulnerabilities.

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. Dr. Kalish works under the mentorship of Marisa Bartolomei, PhD, at Children’s Hospital of Philadelphia, Philadelphia.

Dr. Lin 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.