Adam Cohen

My goal is to improve personalization of cancer medicines and to be able to predict, even before human trials, which tumors will be sensitive to which medicines. I am studying drug sensitivity signatures derived using genomic analysis. These signatures are derived from expression microarrays of tumor cells grown in 3-D culture that are either naive or exposed to drugs. I am currently deriving signatures for histone deacetylase inhibitors and DNA methyltransferase inhibitors. I have initiated a phase I clinical trial of valproic acid in women with newly diagnosed breast cancer, and I will be planning trials of other histone deacetylase inhibitors and DNA methyltransferase inhibitors.

Colleen Druzgal

Colleen is investigating targeted therapies in Ewing's sarcoma (ES), a common bone tumor in children. She is using the Lessnick lab knowledge of the molecular anomalies specific to Ewing's sarcoma to specifically inhibit Ewing's sarcoma. Currently, the focus of the project is on HDAC inhibitors combined with cytarabine, found in previous experiments in vitro to inhibit growth of ES cells in a mouse xenograft model. She hopes to confirm effects of the drugs on tumors by quantifying histone acetylation levels. The ultimate goal, if the combined therapy proves to be effective will be to bring this drug combination to patients with ES.

Marta Fay

I am interested in understanding how translation regulation protects against tumorigenesis. More specifically, my focus is on Pdcd4, a protein well characterized to have tumor suppressor properties. Pdcd4 interacts with the translation initiation complex and is thought to function as a tumor suppressor by inhibiting the translation of a subset of mRNAs. I aim to understand how Pdcd4 is regulated and determine targets that are down regulated by Pdcd4.

Laurie Jackson

I am currently conducting screens to identify novel activators and inhibitors of the bHLHZip transcription factor, MondoA. In response to glucose, mondoA translocates to the nucleus and promotes transcription of genes such as the Thioredoxin-Interacting Protein (TXNIP). Upregulation of MondoA activity decreases glucose uptake. Cancer cells typically use glucose as their primary source for energy. Because of their extraordinary dependence on glycolysis, interference with a cancer cell’s ability to take up glucose could target cancer cells with some specificity.

Mark Lush

ErbB receptors regulate a variety of developmental processes and are upregulated in several human cancers. Our laboratory uses the zebrafish lateral line as a model to study stem cell proliferation, cell migration and sensory hair cell regeneration. We have isolated zebrafish with mutations in erbB2 and erbB3b that show increased lateral line stem cell proliferation and sensory organ number. My research focuses on further characterizing these zebrafish mutants in order to better understand in which cell types ErbB signaling is required and how they function to regulate stem cell proliferation.

Christopher Maxwell

I am studying the genetics of the transition from inflammation to cancer, using inflammatory bowel disease and its transition to colon cancer as a model. Specifically, I am using next-generation RNA sequencing technology to identity a panel of genomic biomarkers for early adenocarcinoma in the colonic mucosa of patients with ulcerative colitis.

Krista Meyer

The ETS family of transcription factors plays a large role in the regulation of gene expression. Several members are known to undergo chromosomal translocations resulting in genetic rearrangements found in prostate cancer. My project investigates the unique properties, structural and functional, of these particular ETS proteins. The translocation event results in over expression of the oncogenic ETS protein and is thought to be an early event in cancer progression. By understanding how these proteins function and what the functional surfaces look like, it may be possible to rationally design therapeutics that specifically inhibit the activity of the ETS protein and stop the transformation process.

Kate Modzelewska

I am using the nematode Caenorhabditis elegans to decipher the intricacies of signaling pathways. Currently, I am focusing my research on a receptor tyrosine phosphatase Clr-1, a member of the LAR family of receptor phosphatases, and its role in EGF receptor signaling. Ultimately, I hope to determine whether an analogous mechanism exists in humans.

Cecinio (Nikko) Ronquillo

Breast cancer metastasis is a very important clinical problem that we face today. Despite its relevance to cancer biology, the mechanisms that govern the metastatic process are largely unknown. Our lab has previously shown that Macrophage Stimulating Protein (MSP) is an important mediator of breast cancer metastasis; however, it is still unknown how MSP drives metastasis. My work focuses on elucidating the mechanism of how MSP promotes breast cancer metastasis in vivo. I will directly test the hypothesis that MSP increases a tumor stem cell population, which in turn is responsible for metastasis. My research will also result in pre-clinical data regarding the effects of inhibition of the MSP pathway in tumor growth and metastasis that may positively affect breast cancer patients.

Raffaella Soldi

Global transcriptional profiling has advanced breast cancer research, facilitating analyses of breast cancer subtypes and prognostic subgroups. While gene expression signatures can identify patients with aggressive tumors who require chemotherapy, data that guides drug selection is relatively sparse. However, treating unselected populations of patients will fail to optimize response rates. We propose a method that incorporates genomic and preclinical testing of patient tumors to identify optimal and novel therapies for individual breast tumors. We provide a drug sensitivity prediction model using primary tumor gene expression profiles and offer preclinical examples of drug response based on this model. This approach can be used to personalize drug therapy for patients with cancer, and also be applied to the study of drug efficacy in other diseases. This union of genomic and preclinical analyses will hopefully improve clinical responses for patients while sparing them toxicity from agents that are ineffective against their tumors.