Edge Awards

The Endowment for the Development of Graduate Education (EDGE) fund was established in early 2009 to support graduate students in units affiliated with the Endowment for the Basic Sciences. Each of the EBS Units (nine of them) contributed $25,000 and these amounts were matched by EB ($225,000) with EBS funds. From this, an endowment was created and we are now soliciting contributions to add to this base to be able to supplement the funding of graduate students in future years. Online donations are being excepted via the secure Michigan Online Giving site.

EBS EDGE Award Winners, 2015

2015 recipients of the Basic Science EDGE award (Endowment for Development of Graduate Education):

Bradley Klemm

Bradley Klemm is a Ph.D. candidate in the Department of Biological Chemistry working with Dr. Carol Fierke. Brad’s thesis is focused on the nuclease protein-only ribonuclease P 1 (PRORP1) from Arabidopsis thaliana. PRORP1 and homologous PRORPs in plants and mammals perform an essential step in the maturation of precursor tRNAs, making their function critical for protein synthesis and cellular/organismal survival. Brad has contributed to our understanding of the active site structure and catalytic mechanism of PRORP1. He is currently elucidating the molecular interactions that the PRORP1 RNA-binding domain uses for substrate recognition. The domain contains pentatricopeptide repeats (PPRs), which are a structurally conserved helix-turn-helix repeating motif found in a large class of single-stranded RNA binding proteins. His research will provide insight into the novel use of PPRs by PRORP1 to instead recognize a complex RNA structure. He has already identified residues crucial for substrate binding and continues to validate interactions required for substrate specificity.

Carpenter

Brandon Carpenter is pursuing his Ph.D. in the Cell and Developmental Biology graduate program under the guidance of Dr. Benjamin Allen. Brandon’s thesis research is focused on understanding the mechanisms that control the trafficking, processing and function of the GLI family of transcription factors, which are key effectors of the Hedgehog signal transduction pathway. Hedgehog signaling is essential for embryonic development as well as adult tissue homeostasis, renewal and regeneration. Conversely, deregulated Hedgehog pathway activity leads to a wide range of human birth defects and cancers. GLI proteins are the transcriptional effectors of the Hedgehog pathway, binding DNA to modulate expression of Hedgehog target genes. Unique to these transcription factors is their trafficking to the primary cilium, a cellular organelle that coordinates signaling from the surrounding environment in nearly all cells of the body. However, it remains unclear why GLI proteins traffic through cilia, and what mechanisms mediate this subcellular transport. Brandon is working to define a novel role for members of the kinesin-2 family of motor proteins in the regulation of GLI protein trafficking and function. Kinesin-2 motor complexes traffic protein cargo within and between different subcellular compartments, including the primary cilium. Brandon has found that kinesin-2 motors directly interact with GLI proteins via specific domains and that disrupting these interactions results in altered GLI protein activity, uncovering a novel role for kinesin-2 proteins in the regulation of GLI transcriptional activity, and shedding light on how kinesin-2 motors bind and transport cargo. Brandon’s research will lay the groundwork for the development of new therapeutic approaches to target GLI/kinesin-2 interactions in a growing number of Hedgehog-dependent pathologies.

Colleen Carpenter

Colleen Carpenter is a PhD candidate in the Department of Pharmacology in the laboratory of Margaret Gnegy. The goal of Colleen’s thesis is to develop inhibitors of protein kinase C that will cross the blood brain barrier and block the action of amphetamine. Working with a chemist at the University of Michigan, Colleen has identified a lead compound that appears to cross the blood brain barrier and inhibit the action of amphetamine to release the reinforcing neurotransmitter, dopamine. She is presently testing if the drug will block the reinforcing behavior of amphetamine with initial success. Colleen is also examining the mechanism by which the drug inhibits protein kinase C which seems to impart a unique selectivity to its action. There is no approved therapy for amphetamine use disorder. Consequently, Colleen’s work could help satisfy the huge unmet need for a therapeutic to treat this debilitating disorder and make a significant contribution to the treatment of addiction.

Jonathan Gumucio

Jonathan Gumucio is a PhD candidate in the Department of Molecular & Integrative Physiology working in Chris Mendias' lab. Jonathan's work is focused on the pathophysiology of myosteatosis, which is the fat accumulation and fibrosis that occurs in degenerative skeletal muscle conditions. He studies the pathways that regulate the accumulation of pathological lipids, the role that these lipids play in exacerbating the degenerative phenotype and the mechanical cues that lead to structural and functional changes in the extracellular matrix. Jonathan has developed innovative and translationally relevant animal models, and integrates biochemical and biophysical techniques from the single cell level up through the whole tissue level in these studies. His work will have an important role in identifying therapeutic targets to improve the treatment of myosteatosis and help to shape the surgical and rehabilitation interventions for patients with chronic degenerative skeletal muscle conditions.

Jhansi Leslie

Jhansi Leslie is a Ph.D. candidate in the Department of Microbiology & Immunology performing her thesis project in the lab of Vincent Young. Jhansi’s thesis work is characterizing the pathogenesis of the bacterium Clostridium difficile. C. difficile infection occurs in patients who have their indigenous gut microbiota disrupted by the administration of antibiotics, which changes the overall environment of the gastrointestinal tract. Jhansi is investigating how C. difficile interacts with the host and bacterial elements of this altered gut environment. To do this, Jhansi is employing both animal models of C. difficile infection and a novel approach using human intestinal organoids to model the gut epithelium. Her work has demonstrated that C. difficile infection results from the complex interaction between the pathogen, the indigenous gut microbiota and the epithelium and immune system of the host. Any disruption of the normal balance of these elements can result in C. difficile colonization, toxin production and resultant colitis. Thus, Jhansi’s work points to a multi-pronged approach that can be used to combat this important healthcare-associated infection

Tomberg

Kärt Tomberg entered the Human Genetics Ph.D. program through the Program in Biomedical Sciences in 2010. She received her B.S. degree in Biology and M.S. degree in Molecular and Cell Biology from the University of Tartu in Estonia with honors. Kärt has a stellar academic record. She received grades of A and A+ in nearly all of the required graduate level courses and earned a GPA of 4.0.

Kärt is performing her dissertation research in the laboratory of Dr. David Ginsburg, who is renowned investigator in the field of blood clotting disorders and an engaged and seasoned mentor. Kärt’s dissertation research is focused on identifying novel genes that impact the severity of venous thrombosis, one of the major causes of morbidity in western society. She has undertaken an extremely ambitious approach to achieve her experimental goals, which involves mutagenizing genetically engineered mice that are predisposed to thrombosis in order to discover new genes that rescue the clotting defects when mutated. Kärt has now successfully completed the genetic screens and recently identified a candidate gene of interest. Her work represents a tour de force of effort and ingenuity, and importantly, her findings have generated much interest and excitement in the field.

Kärt has presented her studies at the International Mammalian Genome Conferences in Salamanca, Spain (2013) and in Bar Harbor, ME (2014) and received the Lorraine Flaherty Award in recognition of her outstanding presentations and research accomplishments two years in a row. Kärt already has three publications from her Master’s research, and her thesis research will culminate in at least one important first author paper and several co-author publications. Her findings will have high impact in both basic science and clinical arenas as her work has potential to provide substantive new insights into the pathways that control blood clotting as well as future therapeutic interventions. In recognition of Kärt’s potential as an independent researcher, she was awarded a prestigious International Fulbright Scholarship and received several awards from the Fulbright Institute in recognition of her research accomplishments. Kärt also successfully competed for an American Heart Association fellowship award.

Yanxiao Zhang

Yanxiao Zhang is a Bioinformatics Program Ph.D. candidate working in the lab of Assistant Professor Maureen Sartor. His thesis work focuses on high-throughput assays. High-throughput biological assays, including microarrays and next-generation sequencing, can quickly generate thousands to millions of measurements per sample. These technologies have greatly impacted biomedical research and increased the rate of new discoveries. However, as these technologies are fast-developing, there is a huge need for better models to enhance the inference from the vast amount of measurements that have been generated and for novel paradigms to integrate multiple datasets to dig out pivotal biological events. His thesis work contributes to this field by focusing on development of a novel analysis method for a popular high-throughput assay (namely ChIP-Seq), and incorporating multiple different datasets to investigate the molecular etiology of two common types of cancers.

EBS EDGE Award Winners, 2014

2014 recipients of the Basic Science EDGE award (Endowment for Development of Graduate Education):

William Law

William Law is a PhD student in the Department of Human Genetics and is performing his thesis research in the laboratory of Anthony Antonellis. The major focus of Bill’s research is to identify regulatory variation important for the development and diseases of the peripheral nervous system. Bill has developed a very clever and efficient pipeline that computationally predicts transcriptional regulatory elements that harbor common single-nucleotide polymorphisms (SNPs). He is then functionally evaluating the regulatory activity of the major and minor SNP alleles in Schwann cells, motor neurons, and muscle cells. Bill’s efforts have already revealed a handful of regulatory SNPs that he is characterizing more deeply by deleting them in cultured cells using CRISPR/Cas9 technology; he has already successfully deleted two regions using this approach. Bill’s research will have major implications for determining the etiology of peripheral nerve disease. Indeed, results will allow us to assess each identified SNP as a genetic modifier of inherited peripheral neuropathy, which displays a high degree of unexplained clinical severity.

Kathryn Livingston

Kathryn Livingston is a PhD candidate in the Department Pharmacology working with Dr. John Traynor. Kathryn’s thesis work is to explore the nature of an allosteric binding site on the mu-opioid receptor, a G protein coupled receptor. This novel site is distinct from the orthosteric site where traditional opioid drugs and endogenous opioid peptides bind. Using cell cultures and purified proteins Kathryn has described a potential mechanism of allosteric modulation that may be generally applicable to other G protein coupled receptors. Kathryn’s work could identify a novel target for pain relieving drugs that might avoid the tolerance and dependence issues
associated with long term opioid therapy.

Mary McCarthy

Mary McCarthy is a PhD candidate in the Department of Microbiology & Immunology, working with Jason Weinberg, MD. Mary’s thesis research is focused on studies of adenovirus pathogenesis, examining interactions between viral infection and host immune responses that contribute to the control of viral infection but also to host damage. Mary has successfully established a mouse model of adenovirus myocarditis, an important cause of human disease that has previously been difficult to study. Her work examines critical host factors such as interferon gamma and the immunoproteasome, defining ways in which those factors contribute to the pathogenesis of adenovirus myocarditis in an effort to establish them as novel therapeutic targets.

Datta Mellacheruvu

Datta Mellacheruvu is progressing towards a PhD in Bioinformatics under the guidance of Dr. Alexey Nesvizhskii. His research is focused on the development of bioinformatics tools for reconstruction of protein-protein interaction networks. The analysis of protein complexes and interaction networks, and their dynamic behavior are of central impor-tance in biological research. Affinity purification coupled with mass spectrometry (AP-MS) technology is now widely used for protein interaction analysis. Datta’s work addresses the critical need for robust computational methods and tools for AP-MS data. The computational tools developed by Datta, most notably the Contaminant Repository for Affinity Purification (www.crapome.org), are already used extensively by hundreds of laboratories worldwide.

Erin Miller

Erin Miller is a pursuing her PhD in the Department of Biological Chemistry with Dr. Patrick O’Brien. Her research is focused on the question of how DNA glycosylases recognize damaged bases in the genome. This is a key question to understanding how cells avoid somatic mutations that can arise from endogenous and exogenous sources of DNA damage. Erin has determined the kinetic mechanism of AlkA, an enzyme that recognizes a wide range of alkylated bases. Comparison of different enzymes that independently evolved to repair alkylated DNA reveals some interesting similarities and differences, helping to explain why organisms require multiple enzymes for repair of alkylation damage.

Maeran Uhm

Maeran Uhm is a PhD candidate in the Department of Molecular & Integrative Physiology working with Dr. Alan Saltiel in the Life Sciences Institute. Maeran has contributed to understand the molecular mechanisms of the non-canonical IKK kinases, IKK and TBK1 in regulating energy homeostasis in adipose tissue. Her research revealed that elevated levels of these two enzymes in obese adipose tissue reduced the ability of fat cells to respond to catecholamines, “fat-burning” hormones generated by the activation of sympathetic nervous system and in turn reduced energy expenditure. She is also currently focusing on the role of these kinases in the regulation of glucose transport in response to the hormone insulin by targeting an evolutionarily conserved tethering complex called the exocyst. Her research will provide new insights into the molecular events underlying insulin resistance in Type 2 diabetes.

Qi

Qi Xiao is a PhD candidate in the Cell and Developmental Biology graduate program working with Dr. Cheng-Yu Lee in the Life Sciences Institute. Qi’s thesis research explores the role of cellular memory in regulating the functional capability of neural stem cells to generate a requisite number of progeny through the production of progenitor cells during brain development. Qi identified and characterized Klumpfuss, one of the four key transcription factors that are required for maintaining the functional identity of neural stem cells that reproducibly generate progenitor cells. She also discovered a highly conserved DNA modifying enzyme that is required for Klumpfuss, as well as three other transcription factors, to maintain the functional identity of neural stem cells that are capable of generating progenitor cells. Lastly, in collaboration with a post-doctoral fellow in the Lee lab, she uncovered an evolutionarily conserved mechanism that maintains the cellular memory of neural stem cells to generate progenitor cells. Qi’s thesis work provides a road map that will allow other researchers to unravel the role of cellular memory in maintains stem cell functions in higher organisms.

EBS EDGE Award Winners, 2013

2013 recipients of the Basic Science EDGE award (Endowment for Development of Graduate Education):

Sara Bondi Cassidy

Sara Bondi Cassidy is a PhD candidate in the Department of Microbiology & Immunology, working with Dr. Mary O'Riordan. Sara's thesis research explores fundamental aspects of cell biology that influence the interaction of microbial pathogens with their host during infection. Sara discovered a novel role for the cell death regulator, caspase-7, in protecting host cells from membrane damage caused by bacterial pore-forming proteins. Membrane damage by pore-forming proteins is common in many different diseases, including infection, autoimmunity and Alzheimer's, and can exacerbate disease symptoms. Sara's studies have implicated caspase-7 and its targets in membrane repair, revealing new potential targets for therapeutics to minimize cellular damage associated with disease-associated pathology. Sara will begin a postdoctoral position with Dr. Julie Segre at the National Institutes of Health in Bethesda, MD in August 2013 studying the biology of the skin microbiome.

Shanshan Cheng

Shanshan Cheng is pursuing her Ph.D. studies in Bioinformatics and Computational Biology under the mentorship of Professor Charles L. Brooks III from the Department of Chemistry and Biophysics Program. Her thesis work centers on characterizing structural properties of viral coat proteins that form the protective shell of viruses, with a focus on delineating features that are exclusive to the virosphere and on structural motifs that determine the size of the assembled architecture. Ms. Cheng's research will aid the rational design of anti-viral drugs that specifically target the pathogen, as well as provide insights on physical principles underpinning successful synthetic maneuvers of the viral templates in various nanotechnology applications.

Jacob Higgins

Jacob Higgins is a PhD candidate in the department of Human Genetics and is doing his dissertation work in the laboratory of Dr. Diane Robins. The focus of Jake's research is on how multiple oncogenic pathways interact with the androgen receptor to determine the initiation and progression of prostate cancer. These studies use bioinformatic tools applied to mouse tumor models to identify key differences between latent and aggressive disease, and cell culture experiments to elucidate mechanisms underlying these differences. Ultimately this molecular characterization may reveal novel biomarkers for disease prognosis and new targets for disease treatment.

Chase Weidmann

Chase Weidmann is progressing towards a PhD in Biological Chemistry under the guidance of Dr. Aaron Goldstrohm. Chase has contributed to the understanding of PUF proteins, a family of RNA binding proteins that regulate genes. His research uncovered new types of switches that turn genes off and regulate the activity of the founding PUF protein, Pumilio. This research will help understand the nature of how RNA-binding proteins like Pumilio act to control protein expression, a major factor in cancer and disease. His work will also advance the engineering of PUFs as therapeutics that regulate genes with adverse effects.

EBS EDGE Award Winners, 2012

2012 recipients of the Basic Science EDGE award (Endowment for Development of Graduate Education):

Luqia Hou

Luqia Hou is a PhD candidate in the department of Molecular & Integrative Physiology working in Dr. Jose Jalife's laboratory. His research focus is on determining molecular mechanism of ventricular fibrillation and developing novel cell therapy for myocardial infarction. In a neonatal rat cardiomyocytes monolayer model, he described the role of hERG, a repolarizing potassium channel, in controlling frequency and stability of reentry arrhythmia. And by transferring three genes into cardiac fibroblasts, he made these cells excitable, coupled with host cardiomyocytes and restored electrical impulse propagation.

Di Ma

Di Ma' is a PhD candidate in the Cell and Developmental Biology graduate program working with Dr. Jiandie Lin in the Life Sciences Institute. In her thesis work, she discovered novel mechanisms that link the biological clock to autophagy regulation, fatty liver disease, and cholesterol homeostasis. Di uses a combination of mouse genetics and biochemical approaches to dissect the pathways that interface circadian timing and metabolism.

Jennifer Gehret McCarthy

Jennifer Gehret McCarthy is pursuing her PhD in the Department of Biological Chemistry with mentoring by Dr. Janet Smith. The focus of her research is the production of terminal alkenes in biosynthesis of natural products and hydrocarbons mediated by a recently discovered sulfotransferase-thioesterase bifunctional enzyme. Her structural and enzymatic studies will aid in developing the enzymes as chemical tools to produce new natural products or to produce hydrocarbons for biofuel. Jennifer will begin a postdoctoral position with Dr. Susan Buchanan at the National Institutes of Health in Bethesda, MD in January 2013.

EBS EDGE Award Winners, 2011

2011 recipients of the Basic Science EDGE award (Endowment for Development of Graduate Education):

Matthew Avenarius

Matthew Avenarius' thesis work has provided important insight into molecular mechanisms of sensory cell development and function and the genetic etiology of human hearing loss. In his thesis work with David Kohrman (Depts. Otolaryngology and Human Genetics) he showed roles for the Grxcr genes in sensory cell maturation using mouse mutants, in controlling the organization and polarity of stereocilia, the actin filament-rich structures critical for mechanotransduction and hearing. In January, 2012, Matthew began a postdoctoral position with Dr. Peter Gillespie at the Oregon Health and Science University.

Tien-Huei Hsu

Tien-Huei Hsu is a PhD candidate in the Department of Microbiology and Immunology working with Dr. Kathy Spindler. Her research focus is on determining host components that are involved in mouse adenovirus type 1 (MAV-1) infection. She uses comparison studies with infection-resistant and susceptible mice, as well as an unbiased genetic approach to identify and investigate the contribution of host factors. The title of her dissertation is "Contribution of Host Factors to Mouse Adenovirus Type 1 Pathogenesis".

Dave Pai

Dave Pai is pursuing a PhD in Biological Chemistry with mentoring by David Engelke. The focus of his dissertation research is the spatial organization of genes in nuclei. Orderly storage of genetic information is essential for its efficient and regulated retrieval, and the specific positioning of genes allows this retrieval to be ordered into pathways. Dave employs molecular genetics and biochemical techniques to investigate the mechanism of three-dimensional localization of specific genes within the nucleus and the consequences of this organization on controlling RNA synthesis.