Aubrey Michi, Ph.D.
Aubrey earned her Ph.D. in Respiratory Medicine from the University of Calgary in 2021. She joined the lab of Dr. Bruce Spiegelman where her research focuses on expanding the repertoire of phosphocreatine functions beyond its established ATP buffering and thermogenic roles. The prevailing paradigm is that most or all cellular enzymes, or protein kinases, utilize ATP for protein phosphorylation. However, phosphocreatine is also an abundant high-energy phosphate which has a phosphate group that makes an energetically favorable leaving group. Aubrey is currently working to identify novel protein kinases that utilize phosphocreatine as a high energy phosphate donor for protein phosphorylation and the biological implications of phosphocreatine-dependent kinase phosphorylation. Using quantitative mass spectrometry and phosphoproteomics, Aubrey has identified numerous mitogen-activated protein kinases (MAPK) that undergo phosphocreatine-dependent phosphorylation. As aberrant MAPK signaling is a hallmark of many cancers, alternative mechanisms driving MAPK signaling may contribute to altered cell proliferation and metastasis. Aubrey joined the CCBM T32 program to obtain the scientific training and career development experiences to achieve her goal of independent investigator studying metabolism and viral infections.
Zachary Sandusky, Ph.D.
Zachary earned his PhD from Vanderbilt University in 2020. He then joined the laboratory of Dr. Myles Brown, where he studies targeted protein degradation of the transcription factor, estrogen receptor alpha (ER) in ER+ breast cancer. His research seeks to better understand the mechanism of action for selective estrogen receptor degraders (SERDs), a new class of ER antagonists that target ER protein for degradation via the ubiquitin-proteasome pathway. Utilizing a functional, genome-wide, CRISPR/Cas9 screening approach, Zachary has identified ubiquitin-proteasome genes that are required for sensitivity to SERDs. He is interested in determining if loss of these ubiquitin-proteasome pathway genes is a mechanism for ER+ breast cancer to develop SERD resistance. Furthermore, Zachary will use his screening approach to identify new therapeutic targets in SERD-resistant ER+ breast cancer. Zachary joined the CCBM T32 training program to prepare for a career as an independent researcher in the fields of oncology and pharmacology. The program will provide essential training support, mentoring, and professional experiences that will supplement his laboratory research and enhance his development as a scientist.
Chelsey LeBlang, Ph.D.
Chelsey earned her Ph.D. in Anatomy & Neurobiology at Boston University School of Medicine in 2020. She joined the lab of Dr. Rosalind Segal in 2021, where she is working to characterize molecular mechanisms underlying axonal degeneration in Chemotherapy Induced Peripheral Neuropathy (CIPN). The Segal Lab has recently described two pathways resulting in calpain-mediated axonopathy in rodent models of CIPN; one due to reduction of axonal bclw protein and the other through the activation of the NAD-ase, SARM1. The goal of Chelsey’s project is to validate the relevance of these pathways in the pathogenesis of human CIPN using a novel human induced sensory neuron model. To assess the effects of chemotherapy treatment on axonal degeneration, she will quantify changes in axonal morphology, calcium flux, bclw and SARM1 protein localization and concentration, calpain activity, and SARM1 metabolite production. She will then test the efficacy of bclw protein mimetic and SARM1 inhibitor treatments previously shown to have a rescue effect in rodent models of CIPN. Chelsey joined the CCBM T32 program to gain the guidance and mentorship needed to complete these metabolomic and chemoproteomic studies, and to attain academic training in the field of cancer chemical biology, which she has not had, due to primary experience in neurobiology. The training she receives in the CCBM T32 program will assist in her goal to identify therapeutic targets in nervous system and immune disorders as an independent researcher.
Mona Sharafi, PhD
Mona earned her PhD from the University of Vermont in 2019. She joined the lab of Dr. Sara Buhrlage in 2021 where she works on the development of highly potent and selective ubiquitin specific protease 28 (USP28) inhibitors by a combined synthetic and computational approach. To advance the deubiquitinating enzyme (DUB) field, the Buhrlage lab has launched a comprehensive campaign to develop reversible and covalent small molecules that target DUB catalytic as well as non-catalytic pockets. However, to date, only a few USP28 small molecule ligands have been reported and shown to promote degradation of c-Myc supporting the notion that pharmacological inhibition of USP28 is a potential novel therapeutic strategy for drugging Myc. Selectivity expected of high-quality probe compounds and a lack of a complex crystal structures has hampered optimization efforts. Therefore, the primary focus of her project is to develop potent and selective inhibitors of USP28. In addition, she will pursue expansion of separate reagents to support target validation studies and leverage the compounds toward other DUB enzymes. T32 training, not only will provide the opportunity to pursue her research and address important challenges in the field but also enhance her mentorship, grantsmanship and technical skills which will position her for a successful career in teaching and independent academic research.
Conor Ronayne, PhD
Conor earned his PhD from the University of Minnesota in 2020. Shortly after, he joined the lab of Pere Puigserver where he studies mechanisms of cell death and cell survival in mitochondrial diseases (MDs). The mitochondria, largely responsible for maintenance of energy, biosynthesis, and redox status, also play important roles in signaling. Hence, defective mitochondrial function has pleiotropic effects in cellular physiology, where mutations in mitochondrial genes can manifest disease phenotypes. Currently, treatment options are limited for patients with MD due to a limited molecular understanding of the disease. In this regard, the Puigserver lab recently identified that inhibition of mitochondrial protein synthesis with tetracyclins rescues mitochondrial disease cells from nutrient deprivation, and delays disease progression in a mouse model of MD. Conor’s project, using biochemical, genetic, and proteomic approaches, seeks to determine the precise mechanism of action toward signaling pathways that initiate at the mitochondrial ribosome upon tetracycline treatment. Conor joined the CCBM T32 training program to gain training in science and career development toward his goal of establishing his own research lab to study metabolism, disease, and therapy.
Erika Portero, PhD
Erika earned her Ph.D. in Chemistry from University of Maryland in 2020. She joined the lab of Dr. Nika Danial where she will investigate the contribution of metabolic alterations to the growth of low-grade gliomas (PLGAs) — the most common brain tumors in children. Many PLGAs go through a relapsing/remitting disease course with major adverse effects on brain development and function. Thus, targeted therapies with reduced neurotoxicity are highly desired. Erika will apply small molecule mass spectrometry approaches to characterize metabolic profiles associated with two prominent BRAF oncogenic drivers in PLGAs. Erika’s research will combine analytical chemistry and biochemical tools to comprehensively map and functionalize metabolic distinctions associated with these oncogenic drivers in order to define actionable metabolic vulnerabilities. She joined the CCBM T32 training program to gain the academic and professional training needed to attain her goal of becoming an independent scientist.
ALUMNI
Benjamin Chandler, PhD
Ben earned his PhD from the University of Michigan in 2020. He joined the lab of Dr. William Kaelin where he investigated degradation of Forkhead Box A1 (FOXA1), a pioneer transcription factor specifically essential in estrogen receptor-positive (ER+) breast cancer. Ben made important steps towards employing gain of signal (or “up”) assays for genetic and chemical screens to identify genetic mediators and pharmacologic compounds that degrade FOXA1. After completing his training in the CCBM program, Ben has transitioned into the role of a Senior Scientist at Odyssey Therapeutics.
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 focused on establishing biological rationales for hematologic malignancy therapy by using novel small molecules as chemical probes. He also investigated the consequences of selective knockdown of the histone lysine demethylase, KDM5A, a transcriptional activator of MYC target genes. Xiaofeng was on the training grant from 2019 to 2021, and is currently Senior Scientist at Cerevel Therapeutics, a biopharmaceutical company focused on developing treatments for neuroscience diseases.
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 investigated pharmacological approaches to treating obesity using a chemoproteomic platform to identify covalent scaffolds that target metabolic proteins. Narek joined the CCBM T32 program in 2019 and received two years of funding thanks to the progress he made in his research. Narek is currently a Principal Scientists at the Novartis Institute for Biomedical Research.
Kedar Puvar, PhD
Kedar earned his Ph.D. from Purdue University in 2020. He joined the lab of Dr. Eric Fischer, where he studied the structural basis of targeted protein degradation. Kedar joined the CCBM T32 program to gain the scientific and professional development training needed to set him up for success in an independent research career. Kedar was awarded an F32 postdoctoral fellowship in 2021, and transitioned into a role in industry in early 2022. He is currently a Senior Scientist at AbbVie, in Targeted Protein Degradation Platform Group.
Matthew Streeter, PhD
Matt earned his PhD from Yale University in 2019. He joined the lab of Dr. Justin Kim where he aimed to develop a platform for the discovery of macrocyclic peptide therapeutics. Matt was part of the CCBM T32 training program in 2020 and received training for a year. He is currently a Scientist II in Discovery Chemistry at Entrata Therapeutics.
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. Laura was part of the CCBM Training Program from 2019 to 2021. Laura is currently a Senior Scientist at AstraZeneca.
Jon Dempersmier, PhD
Jon earned his PhD from the University of Berkeley in 2015. He joined the lab of Dr. Hari Arthanari where he studied the structural basis of transcription factor sequence specificity and function, especially focusing on the interaction of transcriptional activation domains (TADs) with the KIX domains of transcriptional mediators such as MED15. Jon was part of CCBM Training from 2019 to 2021. Currently, Jon is a Scientist II at Rgenta Therapeutics, a company focused on developing small molecule RNA-targeting medicines for cancer and neurological disorders.
Laura Stransky, PhD
Laura earned her PhD from Tuft University in 2017. She joined the lab of Dr. William Kaelin where she investigated 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. Laura developed mouse models and used CRISPR screens and molecular profiling to identify factors associated with HIF2 alpha dependence. She was part of the CCBM T32 training program from 2019 to 2021. Laura is currently a Senior Scientist in Odyssey Therapeutics, a biotech company that is developing next-generation precision medicines for cancer and inflammatory diseases.