Merlin Nithya Gnanapragasam (Nithya), PhD
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 Title: Assistant Professor
 Dept: Biological, Geological and Environmental Sciences
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 Email: m.gnanapragasam@csuohio.edu
 Web: http://www.csuohio.edu/grhd/faculty/merlin-nithya-gna
napragasam
 Address: 2121 Euclid Ave. , Cleveland, OH 44115

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Research Keywords:
Erythropoiesis, Hematopoiesis, Transcription, Transcription factor, Terminal Differentiation, Congenital Dyserythropoietic Anemias, Hemoglobin switching, Fetal Hemoglobin, Sickle Cell Anemia, Beta Thalassemia, Erythroleukemias, post transcriptional regulation.
 
Education:
Ph.D., Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, 2010
M.S., Human Genetics, Sri. Ramachandra Medical College and Research Institute, 2004
B.S., Zoology, Stella Maris College, an autonomous college affiliated to University of Madras, 2002
 
Brief Bio:
Pleased to share a new milestone for our lab team. The first manuscript from our new lab is now online ahead of print @BloodAdvances.

https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2021006730/485478/PUM1-mediates-the-posttranscriptional-regulation

Elagooz R, Dhara AR, Gott RM, Sarah AE, White RA, Ghosh AA, Ganguly S, Man Y, Owusu-Ansa A, Mian OY, Gurkan UA, Komar A, Ramamoorthy M, Gnanapragasam MN. PUM1 mediates the post-transcriptional regulation of human fetal hemoglobin. Blood Advances. 2022 Jun 6; doi: 10.1182/bloodadvances.2021006730. Epub ahead of print. PMID: 35667093.

My scientific interests center on understanding the mechanisms of mammalian erythropoiesis during development and disease. I pursued a strong interest in erythropoiesis during my PhD thesis work on hemoglobin switching, and have continued my investigations on erythropoiesis since. Current studies funded by the NIH, aim to understand how EKLF, a master transcriptional regulator of erythropoiesis, orchestrates the expression of ubiquitous factors regulating DNA replication, and cytokinesis, to cater to the specialized demands of erythropoiesis, and how dysregulation of these pathways contributes to the molecular pathogenesis of severe anemias.

I also continue to pursue studies aimed at understanding the mechanisms of hemoglobin switching. An attractive therapeutic strategy to ameliorate and potentially cure beta thalassemia and sickle cell anemia is to manipulate the globin gene regulation by exploiting the biology behind hemoglobin switching. One of the goals is to identify factors that induce fetal hemoglobin in adult erythroid cells due to its ameliorating effect in these anemias.
 
Honors and Awards:
2018 - 2023 Career Development Award (K01), National Institutes of Health (NIH)
2022 Invitation to talk, Yale¿s YCCEH 2021-2022 Rising Stars in Non-Malignant Hematology Seminar
2022 Invitation to talk, 22nd Hemoglobin Switching Conference, Crete, Greece
2020 - 2022 Cooley's Anemia Foundation Research Fellowship, Cooley's Anemia Foundation
2016 - 2017 Cooley's Anemia Foundation Research Fellowship, Cooley's Anemia Foundation
2020 Invitation to chair the session on Normal and Perturbed Erythropoiesis , Red Cells Gordon Research Conference (Cancelled due to pandemic)
2019 Travel Award (Invited Speaker), Red Cells Gordon Research Conference
2015 Travel Award, Red Cells Gordon Research Seminar
2014 Travel Award, 19th Conference on Hemoglobin Switching
2014 Abstract selected for oral presentation, 19th Conference on Hemoglobin Switching
2011 Roscoe D Hughs Award for excellence in graduate studies, Virginia Commonwealth University
2011 Graduate Student Research Festival Travel Award, National Institutes of Health, Bethesda
2009 Best Student Paper (Second Place), 87th Virginia Academy of Science Annual Meeting
2008 Member of the Phi Kappa Phi Honor Society by election of the chapter at Virginia Commonwealth University, VCU
2004 Distinction (M.Sc.,), Sri Ramachandra Medical College and Research Institute (A Harvard Medical Associated Research Institution), India
2002 Distinction (B.Sc.,), Stella Maris College, an autonomous college affiliated to University of Madras, India
 
Research Interests:
The overarching goal of the laboratory is to delineate the processes that regulate tissue proliferation and differentiation, and how dysregulation of these pathways contributes to human diseases. Our studies utilize erythroid cells as a model system.

Enucleated red blood cells constitute 80% of cells in the body. A precise balance between self-renewal divisions and terminal differentiation is essential for maintaining this enormous pool of cells. Terminal erythroid differentiation is particularly unique in that the differentiation program is coupled to 3-4 rapid terminal cell divisions with peculiarly short G1 phase and fast DNA replication compared to self-renewal divisions. We do not yet understand the processes that regulate the timing, integrity, and the numbers of these rapid terminal divisions. Dysregulation of these terminal divisions leads to impairment of terminal erythroid differentiation and diseases such as Congenital Dyserythropoietic Anemia (CDA), a severe anemia characterized by increased proportions of binucleated erythrocytes.

Our current research goals are twofold: 1) Understand how the specialized transcriptional regulation in erythroid cells ensures that the cell cycle machinery is able to accommodate the rapid pace of the terminal cell divisions. Specifically, our lab will investigate how ubiquitous factors regulating DNA replication, centromere cohesion, and cytokinesis, cater to the specialized demands of the rapid erythroid cell divisions. 2) Investigate the molecular pathogenesis of CDA IV, which is a severe anemia caused by a hypomorphic mutation in EKLF/KLF1 (a master regulator of erythropoiesis), that arises due to a failure in terminal cell divisions and result in binucleate erythroblasts and erythroblasts with DNA bridges.

We are also interested in understanding the mechanisms of hemoglobin switching. An attractive therapeutic strategy to ameliorate and potentially cure beta thalassemia and sickle cell anemia is to manipulate the globin gene regulation by exploiting the biology behind hemoglobin switching. One of our goals is to identify factors that induce fetal hemoglobin in adult erythroid cells due to its ameliorating effects in these anemias.

Ginder GD, Gnanapragasam MN, Mian OY. The role of the epigenetic signal, DNA methylation, in gene regulation during erythroid development. Curr Top Dev Biol. 2008;82:85-116.

Gnanapragasam MN, McGrath KE, Catherman S, Xue L, Palis J, Bieker JJ. EKLF/KLF1-regulated cell cycle exit is essential for erythroblast enucleation. Blood. 2016 Sep 22;128(12):1631-41. (Highlighted in Hematopoiesis News).

Elagooz R, Dhara AR, Gott RM, Sarah AE, White RA, Ghosh AA, Ganguly S, Man Y, Owusu-Ansa A, Mian OY, Gurkan UA, Komar A, Ramamoorthy M, Gnanapragasam MN. PUM1 mediates the post-transcriptional regulation of human fetal hemoglobin. Blood Advances. 2022 Jun 6; doi: 10.1182/bloodadvances.2021006730. Epub ahead of print. PMID: 35667093.
 
Teaching Areas:
Biochemistry, Molecular Biology, Cell Biology
 
Professional Affiliations:
Center for Gene Regulation in Health and Disease and the
Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, OH
Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH
American Society of Hematology
 
Professional Experience:
2021- Member, Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH
2019- Faculty Member, Center for Gene Regulation in Health and Disease, Cleveland State University
2018 - 2019 Research Assistant Professor, Icahn School of Medicine at Mount Sinai, New York, NY
2018 - 2019 Adjunct Lecturer, City University of New York: City College, New York, NY
2015 - 2017 Instructor, Icahn School of Medicine at Mount Sinai, New York, NY
2010 - 2014 Postdoctoral Fellow, Icahn School of Medicine at Mount Sinai, New York, NY. Advisor: Dr. James J Bieker
2005 - 2010 Graduate Research Assistant, Virginia Commonwealth University, Richmond, VA. Advisor: Dr. Gordon Ginder
 
University Service:
2020-  2022 Search Committee Member, Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, OH
2020- 2021  Secretary, Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, OH
2017- 2019  Committee Member, qPCR Advisory Committee, Dean¿s Office of the Icahn School of Medicine at Mount Sinai
2017    Co-organizer, Cell Developmental and Regenerative Biology Department Retreat Organizing Committee
 
Research Grants:
Career Development Award (K01), National Institutes of Health (NIH/NIDDK)
03/01/2018- 01/28/2023
Delineating the functions of EKLF during mammalian terminal erythroid differentiation

The goal of this study is to understand how EKLF, master transcriptional regulator of erythropoiesis, orchestrates the expression of ubiquitous factors regulating DNA replication, and cytokinesis, to cater to the specialized demands of erythropoiesis, and how dysregulation of these pathways contributes to the molecular pathogenesis of Congenital Dyserythropoietic Anemias.



Research Fellowship, Cooley's Anemia Foundation
07/01/2020-06/30/2022
Investigating the post-transcriptional regulation of human fetal hemoglobin by the RNA binding protein PUM1

The goal of this study is to investigate our hypothesis that EKLF directly activates the RNA binding protein PUM1 during terminal erythroid differentiation in part to mediate the post-transcriptional repression of fetal hemoglobin in human adult erythroid cells.



Research Fellowship, Cooley's Anemia Foundation
07/01/16-06/30/18
Genome editing of EKLF enhancer elements for fetal hemoglobin induction

The goal of this study is to perform genome editing of EKLF enhancers to obtain haploinsufficient levels of EKLF, to induce HbF without deleterious effects on other aspects of erythropoiesis.