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Multi-omic analysis of hearing difficulty risk loci and gene regulatory networks in the mammalian cochlea Item Type dissertation Authors Kalra, Gurmannat Publication Date 2021 Abstract The sensory cells of the mammalian cochlea do not have the capacity to regenerate. Studies have identified some genes and pathways that are critical for hair cell formation; however, the conditions necessary to regenerate fully functional hair cells ... Keywords Cochlea; Gene Regulatory Networks; Hair Cells, Auditory; Hearing Loss--genetics; Systems Biology Download date 06/10/2021 23:47:26 Link to Item http://hdl.handle.net/10713/15776 CURRICULUM VITAE GURMANNAT KALRA [email protected] EDUCATION University of Maryland, Baltimore, MD Aug 2016 – May 2021 Ph.D. Candidate, Program in Molecular Medicine, Genome Biology track Dissertation: Multi-omic analysis of hearing difficulty risk loci and gene regulatory networks in the mammalian cochlea Rowan University, Glassboro, NJ Sept 2012- May 2016 B.S. in Biochemistry Magna Cum Laude Bantivoglio Honors Concentration RESEARCH EXPERIENCE Graduate Research Assistant University of Maryland, Baltimore Dec 2016 – May 2021 Project: Investigate the genetics and genomics of hearing loss (HRP Funded, PI: Seth Ament, Ph.D.) • Combine open chromatin data from neonatal mouse with GWAS of hearing difficulty to identify the enrichment of hearing difficulty risk loci in coding and regulatory regions in cochlear epithelial and non-epithelial cells. • Using mouse single cell RNA-seq data, identify differential gene expression in the different cell types in the cochlea and utricle. • Use single cell RNA-seq data to reconstruct and identify gene regulatory networks that drive transdifferentiation of supporting cells to hair cells. Research Assistant Dept of Biological Sciences, Rowan University Sept 2014-Aug 2016 Project: Time-course analysis of gene expression during the S. cerevisiae hypoxic response. (NIH funded, PI: Mark J. Hickman, Ph.D.) • Perform time series analyses on large RNA-sequencing data sets (for ~7000 genes per mutant and dozens of samples—time points and strains) using R. Research Assistant Dept of Bioinformatics, Rowan University Jan 2015-Aug 2016 Project: Binding of Telomeric G-Quadruplex Intercalating Agent: BRACO-19. (PI: Chun Wu, Ph.D) • Perform molecular dynamics simulations on the G-Quadruplex stabilizing drug, BRACO-19, to investigate its DNA binding configurations, using the Schrodinger Molecular Modeling Suite. Research Assistant Dept of Chemistry and Biochemistry, Rowan University Jan 2013- Dec 2013 Projects: Catalytic conversion of biomass-derived sugars into value-added chemicals, Catalytic conversion of 5-hydroxymethyl-2-furfural to furan-2,5-dicarboxylic acid. (PI: K. V. Ramanujachary, Ph.D.) • Implement standard lab procedures, follow protocols as directed, collect sample data using HPLC. SCIENCE ART PUBLICATIONS I make interpretive paintings of biological concepts, inspired by my coursework and research. Website: www.biochemusing.com • Auditory transduction/under the sea. https://biochemusing.com/2020/08/02/auditory-transduction-under-the-sea/ University of Maryland, Baltimore 40th Annual Graduate Research Conference abstract booklet cover. 2018. • Blood brain barrier/ocean shore. https://biochemusing.com/2020/08/02/blood- brain-barrier-ocean-shore/ 1807 An Art and Literary Journal. 2019 ADDITIONAL EMPLOYMENT Medical Scribe ScribeAmerica at Virtua South Jersey Practices July 2015 – Jan 2016 Rotations at Family Medicine, Cardiology, and Breast Clinic • Document patient visit in the Electronic Health Record: transcribing physical exam details and after-visit summary, recording diagnoses, prescriptions, and instructions for follow-up. • Review patient history prior to visit. Resident Assistant Rowan University Res. Learning and University Housing Aug 2013-May 2014 • Directly supervise 36 building residents and assist in conflict resolution. • Run monthly floor meetings, coordinate, administer, and design campus wide programs throughout the year. • Enforce campus policies, assist with upkeep of building facilities, and manage crisis situations. • Participate in on-call nightly duty rotation 1-2 times a week, providing lock- out, emergency services, etc. • Interview new and potential resident assistant candidates. Group Fitness Instructor Rowan University Rec Center Sept 2014 – May 2016 • Conduct weekly dance fitness classes. • CPR Certified LEADERSHIP President, University of Maryland, Baltimore Indian Association 2018-2020 Cultural Secretary, University of Maryland, Baltimore Indian Association 2017-2018 Treasurer, Rowan American Chemical Society 2015- 2016 Secretary, Rowan Bioinformatics Club 2015- 2016 Vice President, Rowan Indian Culture Club 2014-2015 COMPUTER SKILLS Bioinformatics: R, Python, Perl, bash scripting. Typing speed = 75 WPM. PUBLICATIONS • In preparation: Kalra G, Lenz D, Hertzano R, Ament S, Edge A. (2021) Cochlear organoids recapitulate epigenetic and transcriptional programs for the development of hair cells and supporting cells in vivo. • Kalra G, Milon B, Casella AM, Herb BR, Humphries E, Song Y, et al. (2020) Biological insights from multi-omic analysis of 31 genomic risk loci for adult hearing difficulty. PLoS Genet 16(9): e1009025. https://doi.org/10.1371/journal.pgen.1009025. • Mitchell BD, Kalra G, Ryan KA, Zhang M, Sztalryd C, Steinle NI, Taylor SI, Snitker S, Lewis JP, Miller M, Shuldiner AR, Xu H, Increased usual physical activity is associated with a blunting of the triglyceride response to a high-fat meal, Journal of Clinical Lipidology (2018), doi: https:// doi.org/10.1016/j.jacl.2018.11.006. • Machireddy B, Kalra, G, Jonnalagadda S, Ramanujachary K, Wu C. Probing the Binding Pathway of BRACO19 to a Parallel-Stranded Human Telomeric G- Quadruplex Using Molecular Dynamics Binding Simulation with AMBER DNA OL15 and Ligand GAFF2 Force Fields. J Chem Inf Model. 2017 Nov 27;57(11):2846-2864. doi: 10.1021/acs.jcim.7b00287. Epub 2017 Nov 1. PubMed PMID: 29028340. • Bendjilali, N., MacLeon, S., Kalra, G., Willis, S. D., Hossian, A. K. M. N., Avery, E., … Hickman, M. J. (2017). Time-Course Analysis of Gene Expression During the Saccharomyces cerevisiae Hypoxic Response. G3: Genes|Genomes|Genetics, 7(1), 221–231. http://doi.org/10.1534/g3.116.034991 PODIUM PRESENTATIONS • Kalra G, Herb B, Benkafadar N, Janesick A, Milon B, Rose K, et al. Cross- species analysis of gene regulatory networks underlying hair cell regeneration. Association for Research in Otolaryngology Mid-Winter Meeting; 2020; San Jose, CA. • Kalra G, Milon B, Casella AM, Herb BR, Humphries E, Song Y, et al. Biological insights from multi-omic analysis of 31 genomic risk loci for adult hearing difficulty. Association for Research in Otolaryngology Mid-Winter Meeting; 2019; Baltimore, MD. POSTER PRESENTATIONS • Kalra G, Milon B, Casella A, Song Y, Ament S*, Hertzano R.* Genetic Risk for Hearing Difficulty is Enriched in Evolutionarily Conserved Cochlear Enhancers. 2018; Systems Biology Meeting; Cold Spring Harbor Laboratory, NY. • Kalra G, Wu C. Binding challenge for Bevirimat , a HIV maturation inhibitor, to its protein target probed by all-atom molecular dynamics simulation with explicit solvent. 2016; Rowan University STEM Symposium, Glassboro, NJ. • Kalra G, Maurer J, Wu C. Binding of BRACO19 to a telomeric quadruplex, probed by all-atom molecular dynamics simulation with explicit solvent. 2016; Rowan University STEM Symposium, Glassboro, NJ • Kalra G, MacLeon S, Bendjilali N, Hickman M. Defining the Yeast Gene Expression Response to Hypoxic Conditions by Statistical Analysis of RNA-Seq Data. 2015; Genome Informatics Conference; Cold Spring Harbor Laboratory, NY. • Kalra G, MacLeon S, Hickman M. Defining the Yeast Gene Expression Response to Hypoxic Conditions by Statistical Analysis of RNA-Seq Data. 2015; Rowan University STEM Symposium; Glassboro, NJ. • Kalra G, Jain A, Shore A. Catalytic conversion of 5-hydroxymethyl-2-furfural to furan-2,5-dicarboxylic acid. 2014; Rowan University STEM Symposium; Glassboro, NJ. AWARDS AND HONORS American Institute of Chemists Award in Biochemistry Rowan University College of Science and Mathematics May 2016 Summer Program Outstanding Student Research Award Rowan University College of Science and Mathematics July 2015 Dean’s list All semesters, Rowan University 2012 – 2016 Rowan University Scholars Program Scholarship: $56,000 2012 RELEVANT COURSEWORK Mechanisms in Biomedical Sciences (Graduate Program Core Course) Topics in Genome Biology Biochemistry Chemical Biology Biophysical Chemistry Microbiology Anatomy and Physiology 1&2 Cell Biology Genetics of Humans and Model Species Pharmacology Genomics and Bioinformatics Organic Chemistry 1&2 Fundamentals of Biostatistics Research Ethics Programming for Bioinformatics Abstract Title of Dissertation: Multi-omic analysis of hearing difficulty risk loci and gene regulatory networks in the mammalian cochlea Gurmannat Kalra, Doctor of Philosophy, 2021 Dissertation Directed by: Seth A. Ament, Ph.D. Assistant Professor Institute for Genome Sciences. The sensory cells of the mammalian cochlea do not have the capacity to regenerate. Studies have identified some genes and pathways that are critical for hair cell formation; however, the conditions necessary to regenerate fully functional hair cells remain unknown, as the genetic and genomic architecture of hearing loss and hair cell regeneration is only partially defined due to different experimental conditions and models used in each study. This dissertation
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    www.nature.com/scientificreports OPEN Assessment of a complete and classifed platelet proteome from genome‑wide transcripts of human platelets and megakaryocytes covering platelet functions Jingnan Huang1,2*, Frauke Swieringa1,2,9, Fiorella A. Solari2,9, Isabella Provenzale1, Luigi Grassi3, Ilaria De Simone1, Constance C. F. M. J. Baaten1,4, Rachel Cavill5, Albert Sickmann2,6,7,9, Mattia Frontini3,8,9 & Johan W. M. Heemskerk1,9* Novel platelet and megakaryocyte transcriptome analysis allows prediction of the full or theoretical proteome of a representative human platelet. Here, we integrated the established platelet proteomes from six cohorts of healthy subjects, encompassing 5.2 k proteins, with two novel genome‑wide transcriptomes (57.8 k mRNAs). For 14.8 k protein‑coding transcripts, we assigned the proteins to 21 UniProt‑based classes, based on their preferential intracellular localization and presumed function. This classifed transcriptome‑proteome profle of platelets revealed: (i) Absence of 37.2 k genome‑ wide transcripts. (ii) High quantitative similarity of platelet and megakaryocyte transcriptomes (R = 0.75) for 14.8 k protein‑coding genes, but not for 3.8 k RNA genes or 1.9 k pseudogenes (R = 0.43–0.54), suggesting redistribution of mRNAs upon platelet shedding from megakaryocytes. (iii) Copy numbers of 3.5 k proteins that were restricted in size by the corresponding transcript levels (iv) Near complete coverage of identifed proteins in the relevant transcriptome (log2fpkm > 0.20) except for plasma‑derived secretory proteins, pointing to adhesion and uptake of such proteins. (v) Underrepresentation in the identifed proteome of nuclear‑related, membrane and signaling proteins, as well proteins with low‑level transcripts.
  • Molecular Targeting and Enhancing Anticancer Efficacy of Oncolytic HSV-1 to Midkine Expressing Tumors

    Molecular Targeting and Enhancing Anticancer Efficacy of Oncolytic HSV-1 to Midkine Expressing Tumors

    University of Cincinnati Date: 12/20/2010 I, Arturo R Maldonado , hereby submit this original work as part of the requirements for the degree of Doctor of Philosophy in Developmental Biology. It is entitled: Molecular Targeting and Enhancing Anticancer Efficacy of Oncolytic HSV-1 to Midkine Expressing Tumors Student's name: Arturo R Maldonado This work and its defense approved by: Committee chair: Jeffrey Whitsett Committee member: Timothy Crombleholme, MD Committee member: Dan Wiginton, PhD Committee member: Rhonda Cardin, PhD Committee member: Tim Cripe 1297 Last Printed:1/11/2011 Document Of Defense Form Molecular Targeting and Enhancing Anticancer Efficacy of Oncolytic HSV-1 to Midkine Expressing Tumors A dissertation submitted to the Graduate School of the University of Cincinnati College of Medicine in partial fulfillment of the requirements for the degree of DOCTORATE OF PHILOSOPHY (PH.D.) in the Division of Molecular & Developmental Biology 2010 By Arturo Rafael Maldonado B.A., University of Miami, Coral Gables, Florida June 1993 M.D., New Jersey Medical School, Newark, New Jersey June 1999 Committee Chair: Jeffrey A. Whitsett, M.D. Advisor: Timothy M. Crombleholme, M.D. Timothy P. Cripe, M.D. Ph.D. Dan Wiginton, Ph.D. Rhonda D. Cardin, Ph.D. ABSTRACT Since 1999, cancer has surpassed heart disease as the number one cause of death in the US for people under the age of 85. Malignant Peripheral Nerve Sheath Tumor (MPNST), a common malignancy in patients with Neurofibromatosis, and colorectal cancer are midkine- producing tumors with high mortality rates. In vitro and preclinical xenograft models of MPNST were utilized in this dissertation to study the role of midkine (MDK), a tumor-specific gene over- expressed in these tumors and to test the efficacy of a MDK-transcriptionally targeted oncolytic HSV-1 (oHSV).