Ph.D (Biotechnology), MSc. (Biochemistry)

Madhulika Sharma: MSc, PhD.

Assistant Professor (Research)

Department of Internal Medicine

University of Kansas Medical Center (Division of Nephrology and

Hypertension)

Address ****, ********, Lenexa, KS 66216

Telephone 913-***-****

(Home):

Office: 913-***-****

Cell: 913-***-****

Email: ****************@*****.***

Professional Profile

Highly-experienced and dedicated professional with diverse honours and

accolades acquired for various research contributions within the scientific

world. Passionate about broadening scientific understanding and devising

new research proposals. Possesses great analytical and interpersonal

skills, with experience in mentoring students and supervising technicians.

Has experience managing an independent lab. Has ability to execute

scientific projects under limited direction, contributing to the

conception, design, implementation, and interpretation of scientific

research projects. Understands the objective of drug formulations and

discovery. Can easily take responsibility for the data, results, discussion

and conclusion of the assigned studies with limited supervision. Has

contributed to scientific discussions and reports in national and

international meetings as revealed from the publication record and

conferences attended. Has experience of in vitro and in vivo drug studies.

Highly recognised for achievements within the scientific community.

Objective

In search a position in Industry, one which will allow professional

development.

Key Scientific Skills

Expression Studies: Animal Handling:

Immunohistochemistry, Drug formulations and dosage studies in

immunoflourescence, ELISA, Western mice, Generation of transgenic mice,

blotting, Southern blotting, Northern breeding mice and rats, intra-peritoneal

blotting, antibody characterization, injections, genotyping, tailing and

Microscopy tagging, designing and managing in vivo

studies

Protein-DNA Interaction Studies: Protein Biology:

Electromobility shift assays,Chromatin Small scale bacterial and mammalian

immune-precipitations, DNA foot protein expression/purification, protein

printing quantification, and protein-protein

interaction studies using various

chromatographic techniques, pull downs

and immune-precipitations

Cell and Tissue Culture: Molecular Biology:

Developing and maintaining cell lines. RNA, DNA isolation & purification,

Isolation of glomeruli and culture of plasmid preparation, PCR, RT-PCR,

primary podocytes and mesangial cells, southern & northern blotting, restriction

kidney organ culture, stable and digestion, cloning, site directed

transient transfection in mammalian mutagenesis, building expression

cells including nucleofection, drug constructs and vectors for generating

dosage studies, luciferase promoter transgenic mice, protein expression and

reporter based assays, DNA/ protein binding studies.

Immunocytochemistry and Microscopy

Education and Qualifications

PhD: Biotechnology and Experimental Medicne

Postgraduate Institute of Medical Education and Research, India

Doctoral Studying the pathophysiology of Ischemia/ reperfusion injury in

Thesis: patients undergoing coronary artery bypass graft surgery

M.Sc. Biochemistry

College of Basic Sciences, HPKV, India

Thesis: "To study the Biochemical parameters of seed deterioration in

onion and carrots during storage"

B.Sc. Chemistry

Honours: GGDSD College, H.P. University, India

Achievements & Honors

. Provisional patent filed on uses of a novel protein- on October 9th

. Invited Speaker - invited to a prestigious symposium talk at Annual

American Society of Nephrology at a meeting in Atlanta in 2013.

. NIH R01 grant - scored well (missed award due to sequestration, 2013).

. Reviewer- for Internal grant awards for graduate students and post docs,

reviewed grants for Medical Research Council, London, reviewed research

papers for African Journal of Biotechnology, Plos One and Histology and

Histopathology.

. Internal medicine grant award - for project entitled, The role of Notch

signaling in collapsing glomerulopathy;

. Travel grant from the research Institute of Kansas University Medical

Center for upcoming Annual American Society of Nephrology, 2013.

. Lied pilot grant - for project entitled, The role of Notch signaling in

HIV associated Nephropathy

. Postdoctoral Research Training Scholarship - Kansas University Medical

Center

. Travel Grant - to attend annual meeting of American Society of

Nephrology

. Merit Certificate - for standing first in BSc. Chemistry Honours

Proficiency in programs

Microsoft Word, Excel, powerpoint, Adobe photoshop, indesign, acrobat,

endnote

Professional Memberships

American Society of Nephrology

American Physiological Society

Career Summary

2011 - present KANSAS UNIVERSITY MEDICAL CENTRE

Assistant Professor (Research) - Department of Internal

Medicine/Kidney Institute

Working on projects to highlight the importance of context dependent Notch

signaling in different kidney diseases. Also focussed on the role of a

novel protein SSLEP in the pathogenesis of polycystic kidney disease.

1. Endeavouring to prove that inhibition of Notch signaling is an effective

approach in inhibiting the disease progression in HIV associated

nephropathy (HIVAN) and other kidney diseases

2. Studying the role of Notch signaling in poly-cystic kidney disease

(PKD), Notch signalling is poorly defined in PKD, this project has

recently been started and has great potential

3. Studying the role of a novel exosomal protein SSLEP which was found

decreased in urine from polycystic kidney disease patients.

Key Achievements

. In recent studies using immunohistochemistry, immunofluorescence,

Western blots and primary cell culture from autosomal dominant

polycystic kidney patients, preliminary data showed a great potential

for Notch3 signaling playing a major role in the pathogenesis of PKD

(polycystic kidney disease); this is a novel finding since Notch pathway

has never shown to be implicated in PKD. Data presented as poster in

recent ASN meeting in Atlanta

. Used Tg26 mouse model of HIV associated Nephropathy to demonstrate that

Notch is distinctly activated in HIVAN, Designed and managed in vivo

pharmacological inhibition studies in mice and drug dosage studies in

differentiated podocytes, showed that inhibition of Notch pathway in

HIVAN plays a protective role in vivo; that HIV proteins can up-regulate

Notch pathway; and that Notch pathway inhibition can reduce podocyte

proliferation in vitro. (studies published recently in Am J physiol.

Renal Physiol, 2013, as first and corresponding author)

2007 - 2011 Senior Research Scientist

Department of Anatomy and Cell Biology / Physiology and Molecular

Biology

Worked on 3 projects, independent and collaborative: Supervised summer

students and technicians

1. To determine the interaction of Cux1 and Cux2 with Notch pathway

(collaborative)

2. To determine the role of Ouabain in Polycystic kidney disease

(collaborative)

3. To determine the role of Notch pathway in HIV associated Nephropathy

(HIVAN) (independent)

Key Achievements

. Worked in collaboration with post- doctoral mentor, Dr Gregory B Vanden

Heuvel. Reported that: TLE4 binds to Cux-1 and modulates its activity by

binding to p27 promoter and repressing its expression during kidney

development; TLE4 is drastically up-regulated in the presumptive

podocytes of capillary loop staged glomeruli; Cux 1 and TLE4 proteins

are found up-regulated in glomerulosclerotic mouse models

. Reported that Cux1 and Cux2 are regulated by Notch signalling pathway

during kidney development and spinal cord formation, respectively. Used

various molecular biology techniques such as protein-protein

interactions, cloning, mutagenesis, Protein-DNA interactions studies,

chromatin immunoprecipitations, luciferase promoter reporter based

assays in these studies. Results published in "Gene" 2009, "Development"

2009 and "Development" 2008

. Worked in collaboration with Dr Gustavo Blanco to show that Ouabain can

activate the Na,K-ATPase signalosome to induce autosomal dominant

polycystic kidney disease cell proliferation

. Also showed that Ouabain can induce epithelial to mesenchymal transition

in primary cells obtained from ADPKD patients. Results published as

abstract and a paper with first author under preparation and also

published in American journal of physiology renal physiology (2011)

. Worked on HIV-associated nephropathy (independent project)

. Published paper in Aids (2010) to highlight the importance of Notch

signaling in HIVAN pathogenesis - project still in process, with two

papers published thus far

2002 - 2007 Postdoctoral Fellow - Department of Anatomy and Cell

Biology

Worked on homeodomain protein Cux-1, its role in kidney development and

disease, under mentorship of Dr Vanden Heuvel (2002). Supervised

technicians as well as several summer graduate students

Key Achievements

. Gained hands on experience in several biotechniques such as, expression

studies, protein-protein interactions, Protein-DNA interactions,

Demonstrated that ectopic expression of Cux-1 in transgenic mice results

in multiple organ hyperplasia, including increased kidney size.

Experimentally proved that Ectopic expression of Cux-1 is associated

with liver tumors; kidney function disrupted in mice, which developed

glomerulonephritis

. Suggested that Cux-1 may play an essential role in most of the human

kidney disease associated with mesangial cell proliferation and

cytoskeletal changes

. Showed that Cux-1 is increased in ADPKD (Autosomal polycystic kidney

disease) and ARPKD (Autosomal recessive polycystic kidney disease) mouse

models; the mechanisms by which Cux-1 regulates these diseases is

different between the two models. Worked on a project demonstrating how

Cux-1 could be regulated during kidney development; showing that Notch

signaling can induce Cux-1 expression in vivo and in vitro; that the

effector of notch signaling pathway TLE 4 protein interacts with Cux-1

. Demonstrated that Cux-1 can interact with TLE4 and histone deacetylases

to repress the transcription of cylin kinase inhibitor p27. Papers

published in Kidney international (2003 and 2005), Developmental

Dynamics (2004 and 2007), Molecular Carcinogenesis (2005) and Americal

journal of physiology (renal physiology) (2008)

2000 - 2001 MOUNT SINAI SCHOOL OF MEDICINE

Postdoctoral Fellow - Department of Structural Biology and

Biophysics

Joined as a Postdoctoral Fellow in Dr Katherine L.B. Borden's laboratory in

New York to work on the PML (Promyelocytic Leukemia) protein

Key Achievements

. Utilized the techniques such as small scale bacterial and mammalian

protein expression/purification, protein quantification, and protein-

protein interaction studies using GST pull-down assays, characterizing

antibodies, deletion and point mutagenesis, cloning and western

blotting; showing that PML can interact with various homeo-domain

containing proteins to modulate its activities

. Demonstrated that PML can bind to eiF4e in vivo and in vitro and can

result in reducing affinity of eif4E for mRNA, thereby suppressing

oncogenic transformation. Papers published in EMBO journal and journal

of Mol Bio (2001)

1994 - 1995 POST GRADUATE INSTITUTE OF MEDICAL EDUCATION AND RESEARCH,

INDIA Research Fellow - Department of Cardiothoracic and

vascular surgery

Key Achievements

. Worked with human patient samples, isolating macrophages and lymphocytes

and studying various inflammatory markers and biochemical pathways

leading of oxidative injury with major emphasis on oxygen free radicals,

nitric oxide and antioxidant enzymes. The project then was extended as a

PhD dissertation. Published two back to back papers in Molecular and

Cellular Biochemistry (2003) and a book Chapter

Publications

. Tran PV, Sharma M, Li X, Calvet JP.Developmental signaling: Does it

bridge the gap between cilia dysfunction and renal cystogenesis? Birth

Defects Res C Embryo Today. 2014: 102 (2): 159-73.

. Sharma M, Magenheimer LK, Home T, Tamano KN, Singhal PC, Hyink DP,

Klotman PE, Vanden Heuvel GB, Fields TA. Inhibition of Notch pathway

attenuates the progression of human immunodeficiency virus associated

nephropathy. Am J Physiol Renal Physiol. 2013:15; 304(8): F1127-36.

Corresponding author)

. Nguyen T, Jansson K, Sanchez G, Sharma M, Reif GA, Wallace DP and Blanco

VG. Ouabain activates the Na,K-ATPase signalosome to induce autosomal

dominant polycystic kidney disease cell proliferation. Am J Physiol

Renal Physiol. 2011: 301; F897-906

. Kroll MR, Viss ES, Lamb J, Horstman J, Powell A, Van Wyk A, Hinkkala K,

Hoogland T, Schippers M, Shannon S, Carlton CG, Sharma M, Taylor A,

Vanden Heuvel GB, Jelsma TN. Asynchronous Expression of the Homeodomain

Protein CUX1 in Sertoli Cells and Spermatids During Spermatogenesis in

Mice. Biol Reprod. 2010. Oct 27

. Sharma M, Callen S, Singhal PC, Zhang D, Vanden Heuvel GB, Buch S.

Activation of Notch signaling in patients HIV associated Nephropathy.

AIDS. 2010: 24; 2161-2170. (Corresponding author)

. Sharma M, Brantley JG, Vassmer D, Chaturvedi G, Baas J, Vanden Heuvel

GB. The homeodomain protein Cux1 interacts with Grg4 to repress p27 kip1

expression during kidney development. Gene. 2009 Jun 15; 439(1-2):87-94.

(Corresponding author)

. Iulianella A, Sharma M, Vanden Heuvel GB, Trainor PA. Cux2 functions

downstream of Notch signaling to regulate dorsal interneuron formation

in the spinal cord. Development.136(14):2329-34.2009

. Iulianella A, Sharma M, Rey JP, Durnin M, Vanden HeuvelG.B and Paul A

Trainor. Cux2 (Cutl2) regulates neural progenitor differentiation,

neuroblast formation and cell fate determination in the developing

spinal cord. Development 2008 135; 729-741

. Alcalay NI, Sharma M, Vassmer D, Chapman B, Paul, B, Zhou J, Brantley

JG, Wallace DP, Maser RL, Vanden Heuvel GB. Acceleration of polycystic

kidney disease progression in cpk mice carrying a deletion in the

homeodomain protein Cux1. Am J Physiol Renal Physiol. Oct1, 2008

. Alcalay NI, Brantley JG, Sharma M, Gooch JL, Vandenheuvel GB.Ectopic

expression of the homeobox gene Cux-1 rescues calcineurin inhibition in

mouse embryonic kidney cultures. Dev Dyn. 2007 236(1):184-91

. Vanden Heuvel GB, Brantley JG, Alcalay N I, Sharma M, Kemeny G, Warolin

J, Ledford AW and Pinson DM. Hepatomegaly in Transgenic mice expressing

the Homeobox gene Cux-1. Mol. Carcinog. 2005 43 (1) 18-30

. Sharma M, Brantely JG, Alcalay N, Zhou J., Maser RL, and Vanden Heuvel

GB. Differential expression of Cux-1 and p21 in polycystic kidneys from

PKD null and cpk mice. Kidney Int. 2005 Feb 67(2): 432

. Sharma M, Fopma A, Brantley JG, and Vanden Heuvel GB. Co-expression of

Cux-1 and Notch signaling pathway components during kidney development.

Dev Dyn. 2004 Dec; 231(4):828-38.

. Brantley JG, Sharma M, Alcalay N and Vandenheuvel GB. Cux 1 transgenic

mice develop glomerulosclerosis and interstitial fibrosis. Kidney Int.

2003 Apr;63(4):1240-8

. Sharma M, Ganguly NK, Chaturvedi G, Thingnam SKS, Majumdar S and Suri

RK. Cardioprotection mediated by HSP70 during ischemia/reperfusion is

linked to increased CD69 expression and intracellular calcium. Mol Cell

Biochem. 2003 May; 247(1-2):31-6.

. Sharma M, Ganguly NK, Chaturvedi G, Thingnam SKS, Majumdar S and Suri

RK. Release of Pro-inflamatory mediators during myocardial ischemia/

reperfusion in coronary artery bypass graft surgery. Mol Cell Biochem.

2003 May;247(1-2):23-30

. Kentsis A, Elizabeth A, Parez J, Sharma M and Borden KL. The ring

domains of promyelocytic leukemia proteins PML and its viral homolog Z

repress translation by directly inhibiting eukaryotic initiation factor

eIF4E. Journal of Mol Biol. 312(4): 609-23,2001

. Cohen N, Sharma M, Kentsis A, Perez JM, Strudwick S, Borden KL. PML RING

suppresses oncogenic transformation by reducing the affinity of eIF4E

for mRNA. EMBO J. 2001 Aug 15;20(16):4547-59

. Suri RK, Jha NK, Vohra H, Manjari RS, Venkateshwaran R, Sharma M,

Thingnam SKS and Ganguly NK. Role of lymphocyte subsets in pathogenesis

of chronic rheumatic heart disease. Asian Cardiovasc. Thorac. Ann. 1998;

6: 104-107

. Cohen N, Sharma M, Kentsis A, Perez JM, Strudwick S, Borden KL. PML RING

suppresses oncogenic transformation by reducing the affinity of eIF4E

for mRNA. EMBO J. 2001 Aug 15;20(16):4547-59

. Suri RK, Jha NK, Vohra H, Manjari RS, Venkateshwaran R, Sharma M,

Thingnam SKS and Ganguly NK. Role of lymphocyte subsets in pathogenesis

of chronic rheumatic heart disease. Asian Cardiovasc. Thorac. Ann. 1998;

6: 104-107

. Suri RK, Ratna MS, Dhawan V, Gupta A, Gupta R, Sharma K, Thingnam SKS,

Puri GD, Sharma M and Ganguly NK. Reactive oxygen species: enzymatic and

nonenzymate antioxidants in patients undergoing open heart surgery.

Annals New York Academy of Sciences Vol. 793, 1996, 366-70

Book Chapter

. Dhawan V, Ganguly NK, Sharma M, Gupta S and Suri RK. Signal transduction

in coronary artery disease: Role of agents modulating tissue injury.

Adaptation biology and medicine (Vol. 1) Edited by Dr B.K. Sharma, N.

Takeda, N.K. Ganguly and P.K Singal, Narosa Publishing House, p. 51-66

Manuscripts in preparation

. Sharma M, Janson K, Blanco G. Ouabain regulates the expression of

Adhesion proteins and cell-cell interaction in ADPKD cells. In

preparation

. Sharma M, Trisha Home, James P Calvet, Darren Wallace, Robin Maser.

Activation of Notch 3 in mouse models and human polycystic kidney

diseases. In preparation

Abstracts, Workshops, Conferences and Seminars

Invited for an oral symposium presentation at ASN, 2013 Atlanta

. Published abstract: Sharma M, Home T, Magenheimer L, Reif G, Magenheimer

B, Maser R, Wallace D, Calvet JP. "Abnormal upregulation of Notch3 in

polycystic kidney disease. "J. Am Soc Nephrol. 2013: 24

. Published abstract: Sharma M, Magenheimer L, Singhal PC, Hyink D,

Klotman PE, Fields TA, Vanden Heuvel GB. "Inhibition of Notch pathway

attenuates the progression of human immunodeficiency virus associated

nephropathy." J. Am Soc Nephrol. 2012: 23

. Published abstract: Sharma M, Reif G, Wallace D, Blanco G," Ouabain

regulates the expression of Adhesion proteins and cell-cell interaction

in ADPKD cells." J. Am Soc Nephrol. 2011: 22

. Published abstract: Sharma M, Callen S, Singhal PC, Vanden Heuvel GB

"Notch pathway activation in animal models and human HIV associated

nephropathy." J. Am Soc Nephrol. 2010: 21

. Published abstract: Sharma M, Callen S, Zhang D, Singhal PC, Vanden

Heuvel GB, Buch S. "Activation of Notch pathway in HIV associated

nephropathy." J. Am Soc Nephrol. 2009: 20

. Published abstract: Sharma M, Brantley JG, Veurink S, Rodova M, Vanden

Heuvel GB, "Ectopic expression of CUX1 results in activation of

mesangial cells" J. Am Soc Nephrol. 2008: 19. 209A

. Invited seminar in Panacea Biotech (August,2008) (Chandigarh, India) on

topic entitled, The role of TLE4, Cux-1, HDAC interactions in kidney

development

. Published abstract: Sharma M, Brantley JG, Vassmer D, Baas J, Vanden

Heuvel GB, and "Epigenetic regulation of cyclin kinase inhibitor p27

during kidney development". J. Am Soc Nephrol. 2007: 18. 357A

. Oral presentation at BRTP symposium on 5th may 2006, in KUMC, "Co-

expression and interaction of Cux-1 with the groucho homologue TLE-4"

. Published abstract: Alcalay NI, Sharma M, Brantley JG, Veurink S, Rodova

M, Vanden Heuvel GB, "Proteolytic processing of Cux-1 is disrupted in

polycystic kidney disease". J. Am Soc Nephrol. 2006:17. 706A

. Published abstract: Sharma M, Brantley JG, Vassmer D, Baas J, Vanden

Heuvel GB, "Co-expression and interaction of Cux-1 with the groucho

homologue TLE-4." J. Am Soc Nephrol. 2006: 17. 241A

. Published abstract: Sharma M, Brantley JG, Vanden Heuvel GB, "PDGF

induced proliferation of mesangial cells is mediated by upregulation of

Cux-1." J. Am Soc Nephrol. 2005: 16. 599A

. Published abstract: Sharma M, Brantley JB, Ryals JM, and Vanden Heuvel

GB Increased proliferation and apoptosis of mesangial cells isolated

from Cux-1 transgenic mice" J. Am Soc Nephrol 2004: 15: 497A

. Published abstract: Alcalay NI, Brantley JG, Sharma M, Magenheimer BS,

Calvet JP, Vanden Heuvel GB "Ectopic expression of homeobox gene Cux-1

rescues metanephric growth inhibition by cyclosporine A" J. Am Soc

Nephrol. 2004: 15: 675A

. Published abstract: Sharma M, Brantley JB, Vanden Heuvel GB. Co-

expression and interaction of Cux-1 with the groucho homologue TLE-4" J.

Am Soc Nephrol. 2004: 15: 413A

. Published abstract: Vanden Heuvel GB, Brantley JG, Alcalay N, Sharma M,

Maser RL, "Differential expression of Cux1 and p21 in cystic kidneys

from PKD null and cpk mice." J. Am Soc Nephrol. 2002: 13: 115 A

. Poster presentation,"Trying to solve the PML puzzle: Nuclear body

Function in Regulation of RNA Transport" ASPEN Cancer conference. 2001

. Poster presentation "Biochemical agents modulating tissue injury during

ischemia and reperfusion in patients undergoing coronary artery bypass

graft" at Vivek Chander Shekhar Memorial Young Scientist Award, 1999

held at PGIMER, Chandigarh on 5th April, 1999

. Poster presentation "Role of agents modulating tissue injury in coronary

artery disease" at 65th Annual Meeting of the Society of Biological

Chemists (India), 1996

. Poster presentation "Signal transduction in coronary artery disease" at

IV World Congress of Adaptive Medicine held at PGIMER, Chandigarh,

India, 1995

Personal Details

Other: Driver; full clean licence

Interests Cooking, Music and keeping fit.

include: Permanent Resident

Citizenship

Status:

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