Neel H. Shah, PhD

Tyrosine kinases are enzymes that act as “on” and “off” switches for signals in cells and are important in regulating cellular activity, such as cell division. They can become mutated, stuck in the "on" position, and cause unregulated growth of the cell, which is a necessary step for the development of cancer. Kinase inhibitors have been developed as cancer treatments, but they have not been sufficiently effective and are susceptible to drug resistance.  Dr.

Andrew C. Murley, PhD

Dr. Murley is studying how the rapid growth of cancer cells exerts damaging stress on their subcellular compartments. In many cells, chronic stress of one of these compartments, called the endoplasmic reticulum, leads to cell death, but many types of cancer cells are able to avoid this fate. Recent findings point to the existence of secreted molecules released by cells when they are subjected to this stress. These molecules, whose identities are still unknown, can activate processes in neighboring cells, or in the secreting cells themselves, which protect them from this chronic stress.

Roberto Zoncu, PhD

Cancer cell metabolism differs from that of healthy cells because cancer cells have extreme requirements for energy. An organelle inside the cell called the lysosome has recently been defined as a “metabolic signaling center,” which senses cellular nutrient levels and communicates them to a growth regulator protein called mTORC1. Dr. Zoncu proposes to synthesize novel molecules that can specifically disable the lysosomal-mTORC1 signaling pathway as a new means of starving cancer cells and thus blocking tumor growth.

Niranjan Srinivas, PhD

Dr. Srinivas is combining new live imaging technologies, synthetic biology, and mathematical modeling to quantitatively analyze gene expression patterns in space and time during development. Predictive understanding of such patterns and how they go awry during mutations could help us uncover the molecular mechanisms underlying diseases such as cancer. Combining such knowledge with the ability to synthetically alter gene expression patterns could also lead to novel therapeutic approaches.

Mandy M. Muller, PhD

Dr. Muller [HHMI Fellow] is examining Kaposi’s sarcoma-associated herpesvirus (KSHV), a virus associated with lifelong infections. A healthy immune system keeps the virus in check; however, in immunocompromised individuals, KSHV is associated with a number of malignances, including Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castleman’s disease (MCD). KSHV dramatically manipulates the intracellular gene expression environment of its host cell.

Fuguo Jiang, PhD

Dr. Jiang [Merck Fellow] is studying the CRISPR-Cas system, which has been adopted as a robust and versatile platform for genome engineering in human cells as well as other experimental systems. He aims to use a combination of biochemical experiments, mutagenesis, and biophysical approaches to investigate the detailed molecular mechanism of RNA-guided DNA targeting and recognition by CRISPR-Cas9.

Neel H. Shah, PhD

Dr. Shah aims to elucidate structural details of the signaling enzyme ZAP-70, found primarily in immune T cells. Expression of ZAP-70 in other immune cells, B cells, however, is associated with chronic lymphocytic leukemia. Furthermore, loss of ZAP-70 function causes severe combined immunodeficiency; an impaired immune system can increase a patient's susceptibility to tumor development.

Gina V. Caldas, PhD

Dr. Caldas is investigating the mechanisms by which RNA interference (RNAi) related pathways, implicated in cancer primarily through their role in regulating gene expression, contribute to the fidelity of cell division. In addition to major changes in gene expression, a hallmark of many cancers is genome instability and chromosome loss, processes highly related to inaccurate cell division. Using C. elegans as a model system, her goal is to identify new aspects of cell division control that can be targeted for cancer therapy.

Justin M. Crest, PhD

Dr. Crest is studying the mechanical forces between cells and their underlying substrate, or extracellular matrix (ECM). The physical properties of cells and the ECM shape tissues during development and are critical for malignant tumor progression and metastasis. His research will determine which molecules generate and balance the mechanical forces involved in migration and tissue formation and thus identify novel mechanisms of malignancy.