Selected Publications

Differential gene expression profiles between N-terminal domain and ligand-binding domain inhibitors of androgen receptor reveal ralaniten induction of metallothionein by a mechanism dependent on MTF1

Jon K Obst, Nasrin R Mawji, Simon JL Teskey, Jun Wang, Marianne D Sadar

Hormonal therapies for prostate cancer target the androgen receptor (AR) ligand-binding domain (LBD). Clinical development for inhibitors that bind to the N-terminal domain (NTD) of AR has yielded ralaniten and its analogues. Ralaniten acetate is well tolerated in patients at 3600 mgs/day. Clinical trials are ongoing with a second-generation analogue of ralaniten. Binding sites on different AR domains could result in differential effects on AR-regulated gene expression. Here, we provide the first comparison between AR-NTD inhibitors and AR-LBD inhibitors on androgen-regulated gene expression in prostate cancer cells using cDNA arrays, GSEA, and RT-PCR. LBD inhibitors and NTD inhibitors largely overlapped in the profile of androgen-induced genes that they each inhibited. However, androgen also represses gene expression by various mechanisms, many of which involve protein-protein interactions. De-repression of the transcriptome of androgen-repressed genes showed profound variance between these two classes of inhibitors. In addition, these studies revealed a unique and strong induction of expression of the metallothionein family of genes by ralaniten by a mechanism independent of AR and dependent on MTF1, thereby suggesting this may be an off-target. Due to the relatively high doses that may be encountered clinically with AR-NTD inhibitors, identification of off-targets may provide insight into potential adverse events, contraindications, or poor efficacy.

Androgen Receptors in the Pathology of Disease

Nuclear Receptors
Jacky K Leung, Amy H Tien, Marianne D Sadar

Androgen receptor (AR) belongs to the steroid hormone receptor group of ligand-activated transcription factors in the nuclear receptor superfamily. AR mediates the action of physiological and exogenous androgens to regulate the expression of a network of genes in target tissues that are essential for the development and maintenance of the male phenotype and reproductive function as well as the function of numerous other tissues in both males and females. AR is ubiquitously expressed throughout the body. AR is a modular protein that comprises an N-terminal domain (NTD) that contains all of its transcriptional activity, a DNA-binding domain, a flexible hinge region, and a C-terminal ligand-binding domain (LBD). All clinically approved hormonal therapies target the AR LBD, either directly with antiandrogens and selective AR modulators or indirectly by reducing levels of androgens. Pathological conditions related to AR dysfunction involve altered levels of androgens and structural alterations in the AR. These include mutations, polymorphisms in the polyglutamine tract of the NTD, and alternative splicing of AR to yield constitutively active receptors. From the extensive list of AR-related diseases, herein we describe prostate cancer, androgen-insensitivity syndrome, polycystic ovary syndrome, breast cancer, and a few more pathological conditions in more detail.

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Developing Inhibitors to the Amino-Terminus Domains of Steroid Hormone Receptors

Nuclear Receptors
Jon K Obst, Amy H Tien, Marianne D Sadar

Steroid hormone receptors are ligand-activated transcription factors, acting as master regulators of gene expression. Steroid receptors mediate formation of large protein complexes by recruiting coregulatory proteins and transcriptional machinery to specific genomic regions. Unlike the structured ligand-binding or DNA-binding domains, the N-terminal domain (NTD), where many of these protein-protein interactions occur, contains extended regions of intrinsic disorder. Interactions in the NTD and allosteric binding elsewhere induce temporary and reversible changes in the NTD structure, substantially influencing the repertoire of potential binding partners. This structural plasticity is key for the steroid receptors to coordinate intra- and intercellular signals into a tissue specific response. Designing small molecule inhibitors against intrinsically disordered proteins (IDP) in general has proven difficult as structural information is limited. While some progress has been made in this area, only recently has any molecule targeting IDPs progressed beyond the preclinical stage. Here we summarize the discovery and development of sintokamides, niphatenones, and EPI compounds which target the intrinsically disordered NTD of the androgen receptor. These are the first drugs to target the NTD of any steroid receptor, and EPI-506 and EPI-7386 remain the only compounds that bind to an IDP to have been tested in clinical trials.

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Pin1 inhibition improves the efficacy of ralaniten compounds that bind to the N-terminal domain of androgen receptor.

Communications biology, 2021
Leung, Jacky K, Imamura, Yusuke, Kato, Minoru, Wang, Jun, Mawji, Nasrin R, Sadar, Marianne D
Therapies for lethal castration-resistant prostate cancer (CRPC) are an unmet medical need. One mechanism underlying CRPC and resistance to hormonal therapies is the expression of constitutively active splice variant(s) of androgen receptor (AR-Vs) that lack its C-terminus ligand-binding domain. Transcriptional activities of AR-Vs and full-length AR reside in its N-terminal domain (NTD). Ralaniten is the only drug proven to bind AR NTD, and it showed promise of efficacy in Phase 1 trials. The peptidyl-prolyl isomerase Pin1 is frequently overexpressed in prostate cancer. Here we show that Pin1 interacted with AR NTD. The inhibition of Pin1 expression or its activity selectively reduced the transcriptional activities of full-length AR and AR-V7. Combination of Pin1 inhibitor with ralaniten promoted cell cycle arrest and had improved antitumor activity against CRPC xenografts in vivo compared to individual monotherapies. These findings support the rationale for therapy that combines a Pin1 inhibitor with ralaniten for treating CRPC.

Combination therapy with androgen receptor N-terminal domain antagonist EPI-7170 and enzalutamide yields synergistic activity in AR-V7-positive prostate cancer.

Molecular oncology, 2020
Hirayama, Yukiyoshi, Tam, Teresa, Jian, Kunzhong, Andersen, Raymond J, Sadar, Marianne D
Resistance of castration-resistant prostate cancer (CRPC) to enzalutamide and abiraterone involves the expression of constitutively active, truncated androgen receptor (AR) splice variants (AR-Vs) that lack a C-terminal ligand-binding domain (LBD). Both full-length AR and truncated AR-Vs require a functional N-terminal domain (NTD) for transcriptional activity thereby providing rationale for the development of ralaniten (EPI-002) as a first-in-class antagonist of the AR-NTD. Here, we evaluated the antitumor effect of a next-generation analog of ralaniten (EPI-7170) as a monotherapy or in combination with enzalutamide in prostate cancer cells that express AR-V7 that were resistant to enzalutamide. EPI-7170 had 8-9 times improved potency compared to ralaniten. Enzalutamide increased levels of AR-V7 and expression of its target genes. Knockdown of AR-V7 restored sensitivity to enzalutamide, indicating a role for AR-V7 in the mechanism of resistance. EPI-7170 inhibited expression of genes transcriptionally regulated by full-length AR and AR-V7. A combination of EPI-7170 and enzalutamide resulted in synergistic inhibition of proliferation of enzalutamide-resistant cells that was consistent with results from cell cycle and clonogenic assays. In addition, this drug enhanced the antitumor effect of enzalutamide in enzalutamide-resistant CRPC preclinical models. Thus, a combination therapy targeting both the NTD and LBD of AR, and thereby blocking both full-length AR and AR-Vs, has potential for the treatment of enzalutamide-resistant CRPC.

Ralaniten Sensitizes Enzalutamide-Resistant Prostate Cancer to Ionizing Radiation in Prostate Cancer Cells that Express Androgen Receptor Splice Variants.

Cancers, 2020
Banuelos, Carmen A, Ito, Yusuke, Obst, Jon K, Mawji, Nasrin R, Wang, Jun, Hirayama, Yukiyoshi, Leung, Jacky K, Tam, Teresa, Tien, Amy H, Andersen, Raymond J, Sadar, Marianne D
Blocking androgen receptor (AR) transcriptional activity by androgen deprivation therapy (ADT) improves the response to radiotherapy for intermediate and high risk prostate cancer. Unfortunately, ADT, antiandrogens, and abiraterone increase expression of constitutively active splice variants of AR (AR-Vs) which regulate DNA damage repair leading to resistance to radiotherapy. Here we investigate whether blocking the transcriptional activities of full-length AR and AR-Vs with ralaniten leads to enhanced sensitivity to radiotherapy. Combination therapies using ralaniten with ionizing radiation were evaluated for effects on proliferation, colony formation, cell cycle, DNA damage, and Western blot analyses in human prostate cancer cells that express both full-length AR and AR-Vs. Ralaniten and a potent next-generation analog (EPI-7170) decreased expression of DNA repair genes whereas enzalutamide had no effect. FACS analysis revealed a dose-dependent decrease of BrdU incorporation with increased accumulation of γH2AX with a combination of ionizing radiation with ralaniten. An additive inhibitory effect on proliferation of enzalutamide-resistant cells was achieved with a combination of ralaniten compounds with ionizing radiation. Ralaniten and EPI-7170 sensitized prostate cancer cells that express full-length AR and AR-Vs to radiotherapy whereas enzalutamide had no added benefit.

Discovery of drugs that directly target the intrinsically disordered region of the androgen receptor.

Expert opinion on drug discovery, 2020
Sadar, Marianne D

Intrinsically disordered proteins (IDPs) and regions (IDRs) lack stable three-dimensional structure making drug discovery challenging. A validated therapeutic target for diseases such as prostate cancer is the androgen receptor (AR) which has a disordered amino-terminal domain (NTD) that contains all of its transcriptional activity. Drug discovery against the AR-NTD is of intense interest as a potential treatment for disease such as advanced prostate cancer that is driven by truncated constitutively active splice variants of AR that lack the C-terminal ligand-binding domain (LBD).: This article presents an overview of the relevance of AR and its intrinsically disordered NTD as a drug target. AR structure and approaches to blocking AR transcriptional activity are discussed. The discovery of small molecules, including the libraries used, proven binders to the AR-NTD, and site of interaction of these small molecules in the AR-NTD are presented along with discussion of the Phase I clinical trial.: The lack of drugs in the clinic that directly bind IDPs/IDRs reflects the difficulty of targeting these proteins and obtaining specificity. However, it may also point to an inappropriateness of too closely borrowing concepts and resources from drug discovery to folded proteins.

Revealing Metabolic Liabilities of Ralaniten To Enhance Novel Androgen Receptor Targeted Therapies.

ACS pharmacology & translational science, 2019
Obst, Jon K, Wang, Jun, Jian, Kunzhong, Williams, David E, Tien, Amy H, Mawji, Nasrin, Tam, Teresa, Yang, Yu Chi, Andersen, Raymond J, Chi, Kim N, Montgomery, Bruce, Sadar, Marianne D
Inhibition of the androgen receptor (AR) is the mainstay treatment for advanced prostate cancer. Ralaniten (formally EPI-002) prevents AR transcriptional activity by binding to its N-terminal domain (NTD) which is essential for transcriptional activity. Ralaniten acetate (EPI-506) the triacetate pro-drug of ralaniten, remains the only AR-NTD inhibitor to have entered clinical trials (NCT02606123). While well tolerated, the trial was ultimately terminated due to poor pharmacokinetic properties and resulting pill burden. Here we discovered that ralaniten was glucuronidated which resulted in decreased potency. Long-term treatment of prostate cancer cells with ralaniten results in upregulation of UGT2B enzymes with concomitant loss of potency. This has proven to be a useful model with which to facilitate the development of more potent second-generation AR-NTD inhibitors. Glucuronidated metabolites of ralaniten were also detected in the serum of patients in Phase 1 clinical trials. Therefore, we tested an analogue of ralaniten (EPI-045) which was resistant to glucuronidation and demonstrated superiority to ralaniten in our resistant model. These data support that analogues of ralaniten designed to mitigate glucuronidation may optimize clinical responses to AR-NTD inhibitors.

Keys to unlock androgen receptor translocation.

The Journal of biological chemistry, 2019
Tien, Amy H, Sadar, Marianne D
The androgen receptor (AR) is tightly linked to prostate cancer, but the mechanisms by which AR transactivation is dysregulated during cancer progression are not fully explored. Dagar examined AR translocation to the nucleus to identify a link between heat shock protein 90 (HSP90) and protein kinase A (PKA). Their findings provide a potential mechanism of the initiation of AR transactivation and potential targets for developing and refining treatments for prostate cancer.

Enzalutamide and blocking androgen receptor in advanced prostate cancer: lessons learnt from the history of drug development of antiandrogens.

Research and reports in urology, 2018
Ito, Yusuke, Sadar, Marianne D
Enzalutamide is a nonsteroidal antiandrogen for the treatment of metastatic castration-resistant prostate cancer (mCRPC) both before and after chemotherapy. Enzalutamide is more effective than its predecessor bicalutamide, which was analyzed in head-to-head studies of patients with CRPC. This family of nonsteroidal antiandrogens is now comprised of four drugs approved by the US Food and Drug Administration with two investigational drugs in clinical trials. Antiandrogens have been employed clinically for more than five decades to provide a rich resource of information. Steady-state concentration minimums (C{{sub}}min{{/sub}} or trough) in the range of ~1-13 μg/mL are measured in patients at therapeutic doses. Interestingly, enzalutamide which is considered to have strong affinity for the androgen receptor (AR) requires C{{sub}}min{{/sub}} levels >10 μg/mL. The sequence of antiandrogens and the clinical order of application in regard to other drugs that target the androgen axis remain of high interest. One novel first-in-class drug, called ralaniten, which binds to a unique region in the N-terminus domain of both the full-length and the truncated constitutively active splice variants of the AR, is currently in clinical trials for patients who previously received abiraterone, enzalutamide, or both. This highlights the trend to develop drugs with novel mechanisms of action and potentially differing mechanisms of resistance compared with antiandrogens. Better and more complete inhibition of the transcriptional activity of the AR appears to continue to provide improvements in the clinical management of mCRPC.

Inhibition of androgen receptor by decoy molecules delays progression to castration-recurrent prostate cancer.

PloS one, 2017
Myung, Jae-Kyung, Wang, Gang, Chiu, Helen H L, Wang, Jun, Mawji, Nasrin R, Sadar, Marianne D
Androgen receptor (AR) is a member of the steroid receptor family and a therapeutic target for all stages of prostate cancer. AR is activated by ligand binding within its C-terminus ligand-binding domain (LBD). Here we show that overexpression of the AR NTD to generate decoy molecules inhibited both the growth and progression of prostate cancer in castrated hosts. Specifically, it was shown that lentivirus delivery of decoys delayed hormonal progression in castrated hosts as indicated by increased doubling time of tumor volume, prolonged time to achieve pre-castrate levels of serum prostate-specific antigen (PSA) and PSA nadir. These clinical parameters are indicative of delayed hormonal progression and improved therapeutic response and prognosis. Decoys reduced the expression of androgen-regulated genes that correlated with reduced in situ interaction of the AR with androgen response elements. Decoys did not reduce levels of AR protein or prevent nuclear localization of the AR. Nor did decoys interact directly with the AR. Thus decoys did not inhibit AR transactivation by a dominant negative mechanism. This work provides evidence that the AR NTD plays an important role in the hormonal progression of prostate cancer and supports the development of AR antagonists that target the AR NTD.

Non-Genomic Actions of the Androgen Receptor in Prostate Cancer.

Frontiers in endocrinology, 2017
Leung, Jacky K, Sadar, Marianne D
Androgen receptor (AR) is a validated drug target for prostate cancer based on its role in proliferation, survival, and metastases of prostate cancer cells. Unfortunately, despite recent improvements to androgen deprivation therapy and the advent of better antiandrogens with a superior affinity for the AR ligand-binding domain (LBD), most patients with recurrent disease will eventually develop lethal metastatic castration-resistant prostate cancer (CRPC). Expression of constitutively active AR splice variants that lack the LBD contribute toward therapeutic resistance by bypassing androgen blockade and antiandrogens. In the canonical pathway, binding of androgen to AR LBD triggers the release of AR from molecular chaperones which enable conformational changes and protein-protein interactions to facilitate its nuclear translocation where it regulates the expression of target genes. However, preceding AR function in the nucleus, initial binding of androgen to AR LBD in the cytoplasm may already initiate signal transduction pathways to modulate cellular proliferation and migration. In this article, we review the significance of signal transduction pathways activated by rapid, non-genomic signaling of the AR during the progression to metastatic CRPC and put into perspective the implications for current and novel therapies that target different domains of AR.

Sintokamide A Is a Novel Antagonist of Androgen Receptor That Uniquely Binds Activation Function-1 in Its Amino-terminal Domain.

The Journal of biological chemistry, 2016
Banuelos, Carmen A, Tavakoli, Iran, Tien, Amy H, Caley, Daniel P, Mawji, Nasrin R, Li, Zhenzhen, Wang, Jun, Yang, Yu Chi, Imamura, Yusuke, Yan, Luping, Wen, Jian Guo, Andersen, Raymond J, Sadar, Marianne D
Androgen receptor (AR) is a validated drug target for all stages of prostate cancer including metastatic castration-resistant prostate cancer (CRPC). All current hormone therapies for CRPC target the C-terminal ligand-binding domain of AR and ultimately all fail with resumed AR transcriptional activity. Within the AR N-terminal domain (NTD) is activation function-1 (AF-1) that is essential for AR transcriptional activity. Inhibitors of AR AF-1 would potentially block most AR mechanisms of resistance including constitutively active AR splice variants that lack the ligand-binding domain. Here we provide evidence that sintokamide A (SINT1) binds AR AF-1 region to specifically inhibit transactivation of AR NTD. Consistent with SINT1 targeting AR AF-1, it attenuated transcriptional activities of both full-length AR and constitutively active AR splice variants, which correlated with inhibition of growth of enzalutamide-resistant prostate cancer cells expressing AR splice variants. In vivo, SINT1 caused regression of CRPC xenografts and reduced expression of prostate-specific antigen, a gene transcriptionally regulated by AR. Inhibition of AR activity by SINT1 was additive to EPI-002, a known AR AF-1 inhibitor that is in clinical trials (NCT02606123). This implies that SINT1 binds to a site on AF-1 that is unique from EPI. Consistent with this suggestion, these two compounds showed differences in blocking AR interaction with STAT3. This work provides evidence that the intrinsically disordered NTD of AR is druggable and that SINT1 analogs may provide a novel scaffold for drug development for the treatment of prostate cancer or other diseases of the AR axis.

Androgen receptor targeted therapies in castration-resistant prostate cancer: Bench to clinic.

International journal of urology : official journal of the Japanese Urological Association, 2016
Imamura, Yusuke, Sadar, Marianne D
The androgen receptor is a transcription factor and validated therapeutic target for prostate cancer. Androgen deprivation therapy remains the gold standard treatment, but it is not curative, and eventually the disease will return as lethal castration-resistant prostate cancer. There have been improvements in the therapeutic landscape with new agents approved, such as abiraterone acetate, enzalutamide, sipuleucel-T, cabazitaxel and Ra-223, in the past 5 years. New insight into the mechanisms of resistance to treatments in advanced disease is being and has been elucidated. All current androgen receptor-targeting therapies inhibit the growth of prostate cancer by blocking the ligand-binding domain, where androgen binds to activate the receptor. Persuasive evidence supports the concept that constitutively active androgen receptor splice variants lacking the ligand-binding domain are one of the resistant mechanisms underlying advanced disease. Transcriptional activity of the androgen receptor requires a functional AF-1 region in its N-terminal domain. Preclinical evidence proved that this domain is a druggable target to forecast a potential paradigm shift in the management of advanced prostate cancer. This review presents an overview of androgen receptor-related mechanisms of resistance as well as novel therapeutic agents to overcome resistance that is linked to the expression of androgen receptor splice variants in castration-resistant prostate cancer.

An imaging agent to detect androgen receptor and its active splice variants in prostate cancer.

JCI insight, 2016
Imamura, Yusuke, Tien, Amy H, Pan, Jinhe, Leung, Jacky K, Banuelos, Carmen A, Jian, Kunzhong, Wang, Jun, Mawji, Nasrin R, Fernandez, Javier Garcia, Lin, Kuo-Shyan, Andersen, Raymond J, Sadar, Marianne D
Constitutively active splice variants of androgen receptor (AR-Vs) lacking ligand-binding domain (LBD) are a mechanism of resistance to androgen receptor LBD-targeted (AR LBD-targeted) therapies for metastatic castration-resistant prostate cancer (CRPC). There is a strong unmet clinical need to identify prostate cancer patients with AR-V-positive lesions to determine whether they will benefit from further AR LBD-targeting therapies or should receive taxanes or investigational drugs like EPI-506 or galeterone. Both EPI-506 (NCT02606123) and galeterone (NCT02438007) are in clinical trials and are proposed to have efficacy against lesions that are positive for AR-Vs. AR activation function-1 (AF-1) is common to the N-terminal domains of full-length AR and AR-Vs. Here, we provide proof of concept for developing imaging compounds that directly bind AR AF-1 to detect both AR-Vs and full-length AR. {{sup}}123{{/sup}}I-EPI-002 had specific binding to AR AF-1, which enabled direct visualization of CRPC xenografts that express full-length AR and AR-Vs. Our findings highlight the potential of {{sup}}123{{/sup}}I-EPI-002 as an imaging agent for the detection of full-length AR and AR-Vs in CRPC.

An androgen receptor N-terminal domain antagonist for treating prostate cancer.

The Journal of clinical investigation, 2013
Myung, Jae-Kyung, Banuelos, Carmen A, Fernandez, Javier Garcia, Mawji, Nasrin R, Wang, Jun, Tien, Amy H, Yang, Yu Chi, Tavakoli, Iran, Haile, Simon, Watt, Kate, McEwan, Iain J, Plymate, Stephen, Andersen, Raymond J, Sadar, Marianne D
Hormone therapies for advanced prostate cancer target the androgen receptor (AR) ligand-binding domain (LBD), but these ultimately fail and the disease progresses to lethal castration-resistant prostate cancer (CRPC). The mechanisms that drive CRPC are incompletely understood, but may involve constitutively active AR splice variants that lack the LBD. The AR N-terminal domain (NTD) is essential for AR activity, but targeting this domain with small-molecule inhibitors is complicated by its intrinsic disorder. Here we investigated EPI-001, a small-molecule antagonist of AR NTD that inhibits protein-protein interactions necessary for AR transcriptional activity. We found that EPI analogs covalently bound the NTD to block transcriptional activity of AR and its splice variants and reduced the growth of CRPC xenografts. These findings suggest that the development of small-molecule inhibitors that bind covalently to intrinsically disordered proteins is a promising strategy for development of specific and effective anticancer agents.

Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor.

Cancer cell, 2010
Andersen, Raymond J, Mawji, Nasrin R, Wang, Jun, Wang, Gang, Haile, Simon, Myung, Jae-Kyung, Watt, Kate, Tam, Teresa, Yang, Yu Chi, Bañuelos, Carmen A, Williams, David E, McEwan, Iain J, Wang, Yuzhou, Sadar, Marianne D
Castration-recurrent prostate cancer (CRPC) is suspected to depend on androgen receptor (AR). The AF-1 region in the amino-terminal domain (NTD) of AR contains most, if not all, of the transcriptional activity. Here we identify EPI-001, a small molecule that blocked transactivation of the NTD and was specific for inhibition of AR without attenuating transcriptional activities of related steroid receptors. EPI-001 interacted with the AF-1 region, inhibited protein-protein interactions with AR, and reduced AR interaction with androgen-response elements on target genes. Importantly, EPI-001 blocked androgen-induced proliferation and caused cytoreduction of CRPC in xenografts dependent on AR for growth and survival without causing toxicity.

Crosstalk between the androgen receptor and beta-catenin in castrate-resistant prostate cancer.

Cancer research, 2008
Wang, Gang, Wang, Jun, Sadar, Marianne D
The androgen-signaling pathway plays an important role in the development and hormonal progression of prostate cancer to the castrate-resistant stage (also called androgen-independent or hormone refractory). The Wnt pathway and beta-catenin contribute to prostate biology and pathology. Here application of Affymetrix GeneChip analysis revealed the genomic similarity of the LNCaP hollow fiber model to clinical samples and identified genes with differential expression during hormonal progression. The fiber model samples clustered according to the expression profile of androgen-regulated genes to provide genomic evidence for the reactivation of the AR signaling pathway in castrate-resistant prostate cancer. Pathway-based characterization of gene expression identified activation of the Wnt pathway. Together with the increased expression of AR and beta-catenin, there was increased nuclear colocalization and interaction of endogenous AR and beta-catenin in castrate-resistant prostate cancer from castrated mice. Surprisingly, no interaction or colocalization of AR and beta-catenin could be detected in xenografts from noncastrated mice. These studies provide the first in vivo evidence to support aberrant activation of the AR through the Wnt/beta-catenin signaling pathway during progression of prostate cancer to the terminal castrate-resistant stage.


Dr. Adriana Banuelos

Research Associate

Dr. Amy Tien

Research Associate

Dr. Jonathon Obst

Research Associate

Rina Mawji

Lab Manager

Jean Wang

Research Assistant

Teresa Tam

Research Assistant

Jack Jian

Research Assistant


Lauren Deneault

Graduate Student
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