James Cronk – 2016 Peach Award
I received my undergraduate degree from the University of Colorado Boulder in 2008, and entered UVa’s Medical Scientist Training Program in 2009. Since beginning my graduate work in the Kipnis lab in 2011, I have been primarily focused on the role of methyl-CpG binding protein 2 (MeCP2) on immune function. Mutations or duplication of MeCP2 result in Rett syndrome or MeCP2 duplication syndrome, respectively, and both are devastating neurodevelopmental disorders. Our initial work in the Kipnis lab explored the therapeutic benefits of bone marrow transplant in Mecp2-null mice. Since then, we have shown that Mecp2 is an important regulator of macrophage genetic responses, including inflammation, hypoxia, and glucocorticoid signaling. We are currently exploring tissue-specific macrophage functions in the context of Mecp2 deficiency. In regards to MeCP2 duplication syndrome, I am studying a mouse model of influenza infection. MeCP2 duplication patients experience chronic, too often fatal, respiratory infections; we hope to better understand why this occurs and develop therapeutic strategies.
We are pleased to announce that Emily Billings (graduate student in the Casanova lab) is the recipient of this year’s Jill Hungerford Award. This award is provided through a generous endowment by Nancy and Charles (Chick) Hungerford in loving memory of their daughter Jill (Ph.D. ’95 in Cell Biology). It is given annually to one student in the BIMS program, whose selection is based on outstanding scholarship, leadership and service to the community. Congratulations Emily!
Crystal Richardson, a Cell Biology Ph.D candidate in the lab of Doug DeSimone has received a Ruth L. Kirschstein National Research Service Award for Individual Predoctoral Fellows from the National Institutes of Health. “Mechanisms of Collective Cell Migration.” Collective cell migration is necessary for morphogenesis and diseases progression. Cells undergo collective cell migration during wound healing, regeneration, embryonic development, and cancer metastasis. Most cell migration studies have been done on single cells in culture. However, in vivo many cells migrate as groups maintaining contacts with neighboring cells. Often these contacts are required for directional migration. My goal is to understand how cell-cell contacts influence cell polarity to result in directed collective cell migration. A recent finding in our lab demonstrates that application of mechanical force to cell-cell adhesions is sufficient to recruit a network of keratin intermediate filaments to cadherin adhesions and orient protrusions to direct migration. I seek to further understand this biomechanical mechanism by investigating the role of Wnt-Fz/PCP and PDGF signaling in this process. Overall this study will increase our understanding of how cell behaviors are coordinated to produce collective movements.
Soo Shin, a Biomedical Engineering Ph.D. candidate in the lab of Kimberly Kelly has received a National Science Foundation Graduate Research Fellowship. Project Title: Unexpected gain of function for the scaffolding protein, plectin, due to mislocalization in pancreatic cancer. Research Statement: Pancreatic ductal adenocarcinoma (PDAC) is an intractable clinical problem, typically presenting with metastasis at the time of diagnosis and exhibiting profound resistance to existing therapies. Early detection and complete surgical resection offers the best hope for longer survival. Using phage display and functional proteomics, we recently demonstrated that the cytoskeletal linker protein plectin is a robust biomarker for transition between advanced precursor lesion and invasive PDAC. We showed that plectin, normally cytoplasmic, is localized to the cell surface and is overexpressed in PDAC cells. Plectin has been studied extensively in diseases such as epidermolysis bullosa and muscular dystrophy. However, the biological role of plectin in pancreatic cancer has not been studied. Understanding the biology of aberrant localization of plectin to the cell surface may provide insight into a functional role for this important biomarker of PDAC. The overall goal of this project is to 1) determine the role of plectin in PDAC growth and invasion, 2) determine the potential mechanism by which plectin is mislocalized in PDAC and the effects of plectin mislocalization on PDAC, and 3) delineate the signaling cascades involved in plectin-mediated PDAC growth and invasion.
Xiao Chen, a Biomedical Engineering Ph.D candidate in the lab of Frederick Epstein has received a Predoctoral Fellowship from the Mid-Atlantic Affiliate of the American Heart Association.Project Title for the Award: Accelerating Cardiac MR with Intrinsically Motion-Guided Compressed Sensing.Statement: Recently advances from the fields of information technology and image compression have been adapted to the field of medical imaging (magnetic resonance imaging, or MRI, in particular), leading to impressive increases in the speed of MRI image acquisition. The general term for the new technology is “compressed sensing” (abbreviated as CS). Indeed, early results using CS suggest that this technology may revolutionize MRI of the heart. However, a major challenge involves compensating for respiratory motion, which can cause artifacts and distortions in the images. The major problem being addressed by this study is compensating for respiratory motion when accelerating cardiac MRI using CS, which we will accomplish by incorporating motion tracking methods into CS reconstruction algorithms.
Previous Education: B.S., Engineering Physics, Tsinghua University, Beijing, China
Ali Haider Dhanaliwala, a Biomedical Engineering Ph.D candidate in the lab of John Hossack has received a Predoctoral Fellowship from the Mid-Atlantic Affiliate of the American Heart Association. The Project Title for the Award is: “Red Blood Cells as Ultrasound Contrast and Drug Delivery Agents”. Ultrasound is a unique medical imaging modality as it can both image and deliver therapy to the vasculature. Microbubbles are ultrasound contrast agents that improve ultrasound image quality and can enhance drug delivery vehicle. Microbubbles, however, have short in vivo half-life and a small therapeutic payload. Red blood cells (RBCs) have been investigated as an alternative vascular delivery vehicle that have a long in vivo half-life and a large therapeutic payload. RBCs, however, cannot be imaged in vivo and lack an inherent mechanism to trigger drug release. To overcome these limitations I am proposing the development of a new ultrasound contrast agent – acoustically active RBCs – that will combine the ultrasound contrast of microbubbles with the longevity and drug payload of RBCs. Contrast agents with increased longevity will allow continuous ultrasound investigation of phenomena that can take hours to develop. In addition, acoustically active drug delivery vehicles could use ultrasound to trigger drug release in both space and time.
Previous Education: BSE, Bioengineering, University of Pennsylvania
Zegbeh Kpadeh, a Microbiology Ph.D candidate in the lab of Paul Hoffman has received a Robert D. Watkins Fellowship Grant from the American Society for Microbiology. Deciphering the Bifunctional Role of Oxidoreductase DsbA2 in Legionella pneumophila. Legionella pneumohila (Lpn) are small, fastidious, gram negative bacilli that live in aquatic environments as intracellular parasites of free-living protozoa but cause Legionnaires’ disease when aerolized bacteria infect human alveolar macrophage. Lpn displays a dimorphic developmental cycle in which the vegetative replicating bacilli differentiate into metabolically dormant cyst-like planktonic forms, which are known to be resilient and highly infectious. Disulfide bond (DSB) formation is essential for the folding, activity, and stability of many proteins exported from the cytoplasm to the periplasm. The Dot/Icm type IVb secretion system (T4SS) is essential for virulence and mediates delivery of multiple effector proteins into the host cytoplasm. The proper assembly and function of the Dot/Icm T4SS is dependent on correct DSB formation catalyazed by a novel and essential periplasmic DSB oxidoreductase DsbA2 and not by DsbA1, a second nonessential DSB oxidoreductase. This investigation examines the activities and function of a disulfide bond oxidoreductase, DsbA2, which exists as a bifunctional homodimer with both oxidoreductase and protein disulfide isomerase activity. By gaining a better understanding of the activities and function of this protein in Lpn, we hope to gain new insights into the pathogenic processes utilized by Lpn during infection.
Previous Education: BS Biology, Morgan State University