Disease Programs

Cancer Stem Cells

Michael Kahn (Pathobiology):

Dr. Kahn is moving into clinical trials with a candidate drug that kills cancer stem cells. Another compound has the attractive feature of blocking differentiation of stem cells while allowing proliferation, which may be highly useful in developing therapies.

Alvin Liu (Urology)

Normal organ development depends on intercellular communication via diffusible factors and cell contact, without which diseases like cancer may arise. There are over 200 identifiable cell types in our body, plus many more diseased ones. To understand cell biology we need to determine what genes are expressed (transcriptome) by each cell type, and how this expression is altered in disease states. We employ cell sorting to isolate various cell types, including a possible stem cell type, from the prostate, bladder and kidney for analysis. The resultant cell transcriptomes are superior to the more common ones generated from tissues. The sorted cells are also viable and different cell types can be recombined in culture to study the molecular mechanism by which stem cells are induced to become differentiated cells (and the cancer process). Our lab developed the cell sorting strategy for cells of solid tissues and reported the first transcriptomes of individual prostate cell types and a prostate cancer cell type found in primary tumors.

Larry Loeb (Pathology)

We have developed a new methodology to measure mutation frequency in any segment of DNA with unprecedented sensitivity. We can detect in DNA, one single base substitution amongst one billion correct nucleotides. We are desirous of measuring mutation frequency in stem cells and progeny.

Ray Monnat (Pathology and Genome Sciences)

This lab has a strong interest in how lineage-specific biology shapes the pathogenesis of heritable and acquired human disease. We are particularly interested in how defects in the RecQ helicase pathway in stem or progenitor cells might increase the risk of cancer and of clinically important non-neoplastic diseases such as diabetes mellitus, atheroscleorotic cardiovascular disease and osteoporosis in patients with RecQ helicase deficiencies.

Brian Rubin (Pathology)

We have developed a mouse model of gastrointestinal stromal tumor, a mesenchymal neoplasm composed of cells that differentiate towards the interstitial cells of Cajal. Mice harboring an activated /Kit /allele develop neoplasms with 100% penetrance. Since Kit is necessary for the development of the interstitial cells of Cajal, it stands to reason that activation of Kit through mutation, might result in proliferation of stem cells, resulting in a neoplasm. We believe that this model will help us understand how mesenchymal stem cells proliferate. This information could be used to develop methods of expanding populations of mesenchymal stem cells for use in repairing damaged tissues that result from various diseases.

Larry True (Pathology)

This group works with the Liu group on the projet above as well as transcriptome and proteome mediated functional differences in normal and diseased prostate and bladder.

Ray Yeung (Surgery)

Our group focuses on the pathogenesis of a pediatric hamartoma syndrome known as tuberous sclerosis complex. This proliferative disorder affects multiple pluripotent progenitor cells of the central nervous system, heart and kidney. We believe that the underlying signaling pathways (mTOR and b-catenin) play a significant role in regulating cell growth, proliferation, and differentiation of these immature cells. We use a handful of in vitro and in vivo approaches to explore the mechanism of the TSC proteins and their role in cancer and aging.

to top