Celebrating PGG Graduates
Please join us in our celebration as we highlight our PGG graduates.
The profiles are sectioned by degree type:
Doctor of Philosophy
Thesis Title: Targeting Endogenous Homeostatic Mechanisms for the Treatment of Cocaine Use Disorder: Contribution of NR4A1 and Target Gene Expression
Research and Lab Description: The regulation of gene expression underlies many forms of learning and behavior in the mammalian brain. The changes in chromatin and gene expression are collectively referred to as epigenetic phenomena, and they can be extremely long-lasting. This dissertation aims to define the molecular mechanisms whereby a particular transcription factor leads to long lasting changes in chromatin, in the context of cocaine self-administration and abstinence, leading to a deeper understanding of the role of cocaine in mediating persistent gene expression.
Post PhD Plans: Postdoctoral Fellow, Peranteau Lab, Children's Hospital of Pennsylvania
Mentor Comment: Congratulations to Marco Carpenter, the first doctoral student to graduate from the Heller Lab. Marco's dissertation research applied cutting edge approaches in neuroepigenetic editing to define a novel drug target in cocaine addiction, ushering in a new era of drug discovery to the lab.
Thesis Title: Pharmacological Stimulation of the Human Hsp70 Protein Disaggregase System
Research and Lab Description: I completely my dissertation in the lab of Dr. James Shorter in the Department of Biochemistry and Biophysics. Through my research, we uncovered first-in-class small molecules capable of potently stimulating the activity of the Hsp70 protein disaggregase system. My research highlights Hsp70 as a promising molecular target for pharmacologically stimulating cellular proteostasis to combat aberrant protein aggregation in disease.
Post PhD Plans: INSPIRE Post Doctoral Fellow, Department of Molecular Biology and Biochemistry, Rutgers University
Mentor Comment: Edward Chuang is a very talented young scientist. He is sophisticated, hard-working, bright, and skillful. He has made some very exciting findings in his Ph.D. and is a very bright prospect.
Thesis Title: Investigating the Downstream Effectors of the CCM Pathway: A Role for ADAMTS Proteases and Versican Cleavage
Research and Lab Description: The Kahn Lab is interested in signaling pathways in vascular development and disease with a focus on human cardiovascular diseases including cerebral cavernous malformation (CCM). Prior studies in the lab have revealed a CCM-MEKK3-KLF2/4 signaling axis in brain endothelial cells that contributes to CCM disease. My thesis research further investigated the downstream mechanisms by which KLF2/4 drive disease pathogenesis. From this work, we identified secretion of endothelial proteases and cleavage of the extracellular matrix as critical events for CCM formation.
Post PhD Plans: Post Doctoral Fellow, University of Wisconsin, Madison
Thesis Title: Endocannabinoids Protect Against Seizures in Drosophila Melanogaster
Post PhD Plans: Associate, McKinsey & Company
Mentor Comment: The Sehgal lab extends its heartiest congratulations to Jack Jacobs, whose thesis provided a major conceptual advance on the mechanisms underlying endocannabinoid effects on seizures. Jack brought a new area of biomedical research into our lab, and figured out all the approaches and techniques needed to address important questions in it. We’re proud of him and appreciative of his contributions on many levels. In addition to being a creative and rigorous scientist, Jack was a great lab citizen and a big contributor to lab spirit; really fun person to have around. All the best to him.
Thesis Title: Pharmacologic Reversal of DRP1-Dependent Mitochondrial Fragmentation, a Homeostatic Mechanism in Friedreich Ataxia
Research and Lab Description: As a member of Dr. David Lynch's lab, I conducted research on Friedreich ataxia, an autosomal recessive neurodegenerative disease that does not currently have a cure. In patients with this disease, mutations prevent the synthesis of frataxin, a mitochondrial protein that play a critical role in metabolism. Because the mitochondria play a central role in Friedreich ataxia, I investigated mitochondrial dynamics in response to the loss of frataxin. I developed a novel, quantitative method of analyzing mitochondrial dynamics, and using this method, I found that frataxin deficiency causes excessive mitochondrial fragmentation which is dependent upon the activity of Drp1, a GTPase. Fragmentation was prevented or reversed by restoring frataxin or by inhibiting Drp1. Additionally, SS-31, a small molecule that protects mitochondrial lipids from oxidative damage, could similarly reverse mitochondrial fragmentation. These results have implications for both the pathophysiology of Friedreich ataxia and for the role of mitochondrial dynamics in the progression of neurodegenerative disease.
Post PhD Plans: Medical Writer, AdMed Inc.
Mentor Comment: Congratulations Joe! During your time with us, your work was superlative, and you persevered through some of the toughest times. Good luck to you through all the upcoming years.
Thesis Title: PARP-1 Parkinson's Disease: From Molecular and Cellular Mechanisms to Therapeutic Strategies
Research and Lab Description: Our understanding of the progression and mechanisms underlying the onset of Parkinson's disease (PD) has grown enormously in the past few decades. There is now growing evidence suggesting that PARP-1 hyperactivation is involved in driving PD and that poly (ADP-ribose) (PAR) - dependent cell death is responsible for neuronal loss. Our studies show that elevated intracellular levels of PAR promote the transition of αSyn into higher molecular weight forms. We report that PAR-pαSyn interactions are predominant in pathological states. Moreover, we confirm that the interactions between PAR and αSyn involve electrostatic forces between negatively charged PAR and lysine residues on the N-terminal region of αSyn. In addition, we report on the neuroprotective properties of a low toxicity PARP inhibitor using in vitro neuronal cell cultures. We show that this inhibitor not only protects neuronal cells from DNA damage and oxidative stress, but also protects against NAD+ depletion due to αSyn toxicity. Altogether, our work emphasizes the need to design and validate PARP-1 inhibitors with optimal physicochemical properties for complex neurological conditions, these pharmacological interventions may provide an alternative therapeutic approach for managing PD onset and progression.
Post PhD Plans: I will be working at Merck KGaA – MilliporeSigma as part of their GoGlobal - Life Science, Actives & Formulations program in the antibody-drug conjugate (ADC) group.
Mentor Comment: Laura is a very bright, hard working person with an incredibly upbeat personality. It is impossible to be in a bad mood around her. She will be a success in whatever endeavor she pursues. It was a pleasure serving as her PhD mentor.
Thesis Title: Mechanisms for the Attenuation of White Matter Abnormalities Due to HIV Infection and Antiretroviral Therapies
Research and Lab Description: Lindsay’s thesis work focused on understanding mechanisms that mediate white matter loss due to HIV infection and antiretroviral therapies. Lindsay’s work showed that soluble factors produced by HIV-infected cells or antiretroviral compounds negatively affect oligodendrocytes ability to mature, which may play a role in the persistence of white matter loss observed in HIV-positive individuals with neurocognitive dysfunction. Lindsay is especially interested in developing therapeutics to combat neurodegenerative and demyelinating diseases and understanding the interplay of organellar stress mechanisms that influence neuroinflammation and neurodegeneration.
Post PhD Plans: Starting in summer 2021, Lindsay will continue her scientific career as a postdoctoral research fellow in the Parkinson’s disease research group at AbbVie in Cambridge, MA.
Mentor Comment: One of the best parts of mentoring PhD students is watching their transition from aspiring scientists to full-fledged independent researchers. Your trajectory has been especially remarkable because you came to us straight out of college with not much experience in cell biology and, in rapid succession, learned the necessary technical skills, analytical skills and finally how to use your in-born leadership skills to teach and mentor others. You quickly wowed us with your ability to succeed at projects where other, more senior people, had failed. In the process of writing your first manuscript, you became so fluent with the literature that you could cite chapter and verse. Your analytical skills sharpened as you progressed through your studies. You trained nearly every summer student and undergrad that even came near our labs. You superbly organized BGS interest and support groups to make the graduate school experience better for others. And finally, you even stayed around after defending your thesis for 7 months to finish projects and gather data and find direction for a future project. What else could we ask for? You have been a tremendous colleague and so, of course, we are sorry to see you go but are excited for the next chapter of your progression to senior scientist. Congratulations on all you have accomplished. We hope you stay in close touch with us.
Combined Degree, MD-PhD
Thesis Title: Designing Synthetic DNA Encoded Immunotherapeutics and Nanoparticle Vaccines for Enhanced Immune-Mediated Protection
Research and Lab Description: During his PhD training, Ziyang worked at David Weiner’s laboratory on approaches to deliver immunogens and immunotherapies in vivo through the use of synthetic nucleic acid and adaptive electroporation. He discovered a novel strategy to deliver next-generation DNA-launched nanoparticle vaccines in vivo with enhanced adaptive immunity and reduced dose requirement. He has successfully applied this concepts to infectious diseases (SARS-CoV-2, HIV, and influenza) and cancer (melanoma) models. Ziyang aspires to become a physician investigator who works on the development of vaccines for melanoma and non-melanoma skin cancers in the future.
Post PhD Plans: Ziyang Xu is currently a post-doctoral research fellow at the University of Pennsylvania and an MD-PhD candidate in the graduating class of 2022.
Mentor Comment: Ziyang was a force in the lab who contributed impactful and original scientific contributions to the field of synthetic nucleic acid vaccines as well as the development of novel immunotherapies. Importantly, Ziyang was always available to help others with aspects of their work supporting collaborations on diverse projects. It was as an exciting experience to have him in the laboratory. I am very much looking forward to seeing the next phase of his career and to watch him lead translational medicine by example.