Laura Stevens, PhD

Laura earned her PhD from Yale University in 2017. She joined the lab of Dr. Kornelia Polyak  where she studies stromal-induced heterogeneity of tumors and epigenetic regulation in therapeutic resistance.  She has generated a reporter system that marks cancer cells that are in direct contact with stromal cells, facilitating the purification of these cells from bulk tumors and subsequent functional analyses. She will compare stroma-contact and no-contact cells to identify genes and pathways driven by spatial proximity to stroma and will test several hypotheses. These include the hypothesis that stroma can affect tumor cell phenotypic and epigenetic heterogeneity to promote the evolution of therapy resistant clones and the hypothesis that the stroma is regulating tumor cell epigenetics by altering the metabolome. Laura’s career goals include establishing her own lab, and she has joined the CCBM T32 training program to get the mentorship and career development to help her progress to an independent scientist. The program will expand her knowledge of scientific approaches and state-of-the-art technologies in cancer chemical biology and metabolism in support of her primary research interests.

Jon Dempersmier, PhD

Jon earned his PhD from the University of Berkeley in 2015. He joined the lab of Dr. Hari Arthanari where he studies the structural basis of transcription factor sequence specificity and function.  Many transcription factors contain intrinsically disordered regions (IDRs), which are not amenable to structural analyses via X-ray crystallography or cryo EM.  These IDR regions also harbor mutations found in cancer, but the roles these regions play in normal cellular function and the roles cancer associated mutations play in disease are not understood. The Arthanari lab is a pioneer in the use of nuclear magnetic microscopy (NMR) for structural studies of IDRs, and Jon will be using the structural clues identified by NMR in a host of transcription factor IDRs to interrogate the roles of these regions. In addition he will be investigating the interaction of transcriptional activation domains (TADs) with the KIX domains of transcriptional mediators such as MED15.  These studies will inform small molecule drug design to address aberrant transcription factor activity in cancer cells.  Jon joined the CCBM T32 training program to prepare for a career as an independent investigator. The program will provide support, mentoring and exposure to state-of-the-art technologies and set him on a path toward developing a platform to interrogate transcription factors that he will use as the basis for the work of his own lab.

Laura Stransky, PhD

Laura earned her PhD from Tuft University in 2017. She joined the lab of Dr. William Kaelin where she is investigating the molecular basis of heterogeneous dependence of clear cell renal carcinoma cells (ccRCC) on Hypoxia Inducible Factor (HIF)2 alpha in preclinical models and the clinic. Von Hippel-Lindau gene (VHL) inactivation is an early event in most cCRCC tumors. Loss of VHL leads to an accumulation of the alpha subunits of the HIF transcription factor, a master regulator of hypoxia-inducible genes and a driver of a pro-survival gene expression program. HIF2 alpha inhibitors show some effect against ccRCC, but the response is variable. Understanding the basis of the heterogeneous response will allow the development of predictive biomarkers of response and resistance and enable the design of strategies to circumvent resistance. Laura is developing mouse models and using CRISPR screens and molecular profiling to identify factors associated with HIF2 alpha dependence.  She joined the CCBM T32 training program to gain both scientific training and career development experiences essential to her goal of becoming an independent scientist leading her own research group in the study of cancer signaling.

Narek Darabedian, PhD

Narek earned his PhD from the University of Southern California in 2019. He joined the lab of Dr. Ed Chouchani where he will investigate pharmacological approaches to treating obesity. Activation of calorie-burning (thermogenesis) in brown and beige adipose tissues (BAT) is protective against obesity and may also reduce obesity-related cancer risk. Uncoupling protein 1 (UCP) is the major effector of thermogenesis in BAT but has so far not been pharmacologically targeted. The Chouchani lab discovered that covalent modification of UCP1 cyteine-253 can induce the calorie burning activity of this protein. In collaboration with Dr. Nathanael Gray, Narek will use a chemoproteomic platform to identify covalent scaffolds that target UCP1 cysteine-253.  He expects to identify at least 20 scout molecules and will subsequently use structure activity relationship (SAR) optimization to generate potent and selective drug candidates. He will test candidates for effectiveness in mouse models and human adipocyte cell cultures. Narek joined the CCBM T32 program to get the training he needs to accomplish his research goals of treating obesity and to prepare him to be independent researcher studying a broad set of questions in metabolism and disease.

Matthew Streeter, PhD

Matt earned his PhD from Yale University in 2019. He joined the lab of Dr. Justin Kim where he aims to develop a platform for the discovery of macrocyclic peptide therapeutics. Macrocyclic peptides offer properties that bring to bear several key benefits of other therapeutic modalities. Similarly to small molecules, macrocyclic peptides can be optimized for cell-permeability and oral bioavailability, and similarly to antibody-based therapeutics, they can adhere to relatively flat and featureless protein surfaces. In combination, these properties make macrocyclic peptides ideal for therapeutic targets that are often recalcitrant to small-molecule- and antibody-based therapeutics, such as intracellular protein-protein interactions. Matt will begin construction of peptidic libraries containing homodetic peptides and move toward incorporation of synthetic, natural-product-inspired building blocks. With this large pool of amino acids, the generated libraries will achieve rapid structural diversity that is unparalleled within currently available peptide discovery platforms and should aid in achieving therapeutic endpoints. Matt joined the CCBM T32 training program to learn as much as he can during his time at DFCI while being a part of a great community of scholars.

Xiaofeng Zhang, PhD

Xiaofeng earned his PhD from the University of Massachusetts Boston in 2019. He joined the lab of Dr. Jun Qi where his research focuses on establishing biological rationales for hematologic malignancy therapy by using novel small molecules as chemical probes. Dysregulation of a master oncogene, the MYC transcription factor is implicated in the pathogenesis of multiple myeloma (MM).  Although dysregulation of MYC has been shown to transform cells in culture and to induce MM in transgenic mouse models, the mechanism by which aberrant MYC transcriptional program leads to MM in humans is not well understood. In collaboration with the Anderson laboratory, he will investigate the consequences of selective knockdown of the histone lysine demethylase, KDM5A, a transcriptional activator of MYC target genes. This may prove to be a valuable strategy to regulate MYC expression in MM. He will develop and validate innovative and selective KDM5A inhibitors and degraders by using iterative medicinal chemistry combined with structural and computational biology. Xiaofeng joined the CCBM T32 program to obtain scientific training and career development experiences to achieve his career goal of independent investigator.  The program will provide support, training and mentoring to enrich his knowledge of state-of-the-art technologies and approaches in cancer biology and metabolic science, and identify steps toward achieving his career goals.