Education and Training

Postdoctoral Training. (2006-2010: Microbiology and Immunology)

Dept. of Microbiology and Immunology, University of Texas Medical Branch (UTMB), Galveston, TX, USA

Ph.D. (2002-2006: Radiation and Cancer Biology)

Dept of Biosciences, Himachal Pradesh University, Shimla and School of Life Sciences, Jawaharlal Nehru University (JNU), New Delhi, India

M.Phil. (2000-2002: Radiation and cancer biology)

Dept of Biosciences (HPU, Shimla) and School of Life Sciences, Jawaharlal Nehru University (JNU), New Delhi, India

M.Sc. (1998-2000: Zoology)

Dept of Biosciences, Himachal Pradesh University, Shimla, Himachal Pradesh, India

B.Sc. (1995-1998: Zoology, Botany and chemistry)

St Bede’s College, Shimla, Himachal Pradesh

Research training/fellowships

A. Positions and Honors

Positions Held

2012-till date

Assistant Professor, Center for Biosciences, Central University of Punjab, Bathinda, Punjab, India

2010-12

Research Scientist, Dept. of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA

2006-10

Postdoctoral Research Fellow Dept. of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA

2004-2006

Council for Scientific and Industrial Research (CSIR)/UGC- Senior Research Fellowship, New Delhi, India

2002-04

Council for Scientific and Industrial Research (CSIR)/UGC- Junior Research Fellowship, New Delhi, India

Honors

2012

Judge at Galveston County Science Fair at Moody Gardens Convention Center, Galveston

2011

Facilitator for the small group discussion for the Cell Biology course for medical students.

2011

Yun A. Coronado, summer student working with me won Best poster presentation in Medical Student Summer Research Program (MSSRP), at UTMB, June 2011.

2011

Judge at Medical Student Summer Research Program (MSSRP), UTMB, June 2011.

2010

Second prize for oral presentation in “National Postdoc Appreciation Week”, symposium at UTMB, September 2010.

2009

First prize in poster presentationin “International Education Week”organized by PAHO/WHO Collaborating Center for Training in International Health at UTMB, Galveston

2009

Travel award through the Burroughs Wellcome Trust to attend the 109th General Meeting, American Society for Microbiology, Philadelphia

2008

Travel award through the Burroughs Wellcome Trust to attend the 108th General Meeting, American Society for Microbiology, Boston, Massachusetts.

2007

Best poster award for “Correlation of chronic inflammation and seropositivity in chagasic human serum”.Summer Undergraduate Research Program Poster Presentation. August 2007, University of Texas Medical Branch, Galveston, Texas, USA.

2004-2006

Council for Scientific and Industrial Research (CSIR)/UGC-Senior Research Fellowship, New Delhi, India

2002-2004

Council for Scientific and Industrial Research (CSIR)/UGC- Junior Research Fellowship, New Delhi, India

2002

Qualified NET-LS

1995-1998

Merit Fellowship from Himachal Pradesh University, St Bede’s College (Convent of Jesus & Mary), Shimla, India

Other Experience and Professional Memberships

2012

Reviewer “Revista do Instituto de Medicina Tropical de São Paulo”

2011-till date

Reviewer American Journal of Tropical Medicine and Hygiene

2011-till date

2010 Reviewer Journal of Biomedicine and Biotechnology

2010

Member International Society for Infectious Diseases (ISID)

2010-till date

MemberInternational Society for Heart and Lung Transplant (ISHLT)

2009

Certified for teaching and mentoring (Bromberg workshop in teaching and mentoring at UTMB, Galveston)

2008-till date

Member American Society for Microbiology

2007-till date

Member Society for Free Radical Biology and Medicine

2007

Member American Heart Association

2006

Certified “Basic Radiation Safety in the Laboratory”. University of Texas Medical Branch, Galveston, Texas, USA

B. Peer-reviewed and International Publications

1

Dhiman M, Paola M. Zago, Sonia Nunez, Heidi Spratt, Yun A. Coronado Federico Nunez-Burgio and Nisha Jain GargClinical significance of peripheral blood markers in predicting T. cruzi infection and Chagas disease in human patients. Submitted to Journal of Infectious Diseases (June 2012)

2

Dhiman M, Paola M. Zago, Sonia Nunez, Federico Nunez-Burgio and Nisha Jain Garg. Cardiac-oxidized Antigens Are Targets of Immune Recognition by Antibodies and Potential Molecular Determinants in Chagas Disease Pathogenesis. Plos One (2012) 7; (1):e28449. Impact Factor (IF): 4.4

3

Dhiman M and Garg NJ. Inhibition of NADPH-oxidase Attenuates T cruzi-induced Cardiac Pathology. Journal of Pathology (2011) Dec; 225(4):583-96. (IF): 7.2

4

Jose´ E. Aparicio-Burgos, Laucel Ochoa-Garcia, Jose´ Antonio Zepeda-Escobar, Shivali Gupta, Dhiman M, Jose´ Simon Martinez, Roberto Montes de Oca-Jimenez, Margarita Val Arreola, Alberto Barbabosa-Pliego, Juan C. Vazquez-Chagoyan, Nisha Jain Garg. Testing the Efficacy of a Multi-Component DNA-Prime/DNA-Boost Vaccine against TrypanosomacruziInfection in Dogs. PLoSNegl Trop Dis (2011) 5(5): 1-10. (IF): 4.2

5

Wen JJ, Gupta S, Guan Z, Dhiman M, Condon D, Lui CY, Garg NJ (2010). Adjunct Therapy Controlled the Mitochondrial Oxidative Stress and Arrested the Evolution of Chronic Cardiomyopathy in Benzonidazole-treated Chagasic Rats, J Amer College Cardiology. 2010, 55(22):2499-508. (IF): 11.0

6

Dhiman M, Jasmine Pando, Estrada-Franco JG, Aguilar FR, Corzo SB, Perez GM, Sandoval RG, Garg NJ. Increased myleoperoxidase activity and protein nitration are indicators of inflammation in chagasic patients. Clinical and Vaccine Immunology, 2009, 16(5): 660-666. (IF): 3.27

7

Dhiman M, Nakayasu ES, Hosakote YM,Reynolds BK, Wen JJ, Almeida IC and Garg NJ. Enhanced Nitrosative Stress during Trypanosomacruzi Infection Causes Nitrotyrosine Modification of Host Proteins. Implications in Chaga’s disease. Am J Pathol. (2008) 173 (3): 728-740. (IF): 6.65

8

Dhiman M*, Wen JJ*,and Garg NJ. Tissue-specific oxidative imbalance and mitochondrial dysfunction during Trypanosomacruzi infection in mice. Microbes Infect. (2008) 10 1201-1209. *Equal Contribution (IF): 3.5

9

Deep G, Dhiman M, Mendiz E, Rao AR and Kale RK. Chemo preventive Effects of Mustard Seeds in Chemically Induced Fore stomach and Uterine Cervix Tumors in Murine Model System. Human & Experimental Toxicolgy. (2005) 24 (6): 303-312.

10

Deep G, Dhiman M, Rao AR and Kale RK.Chemopreventive Potential of Triphala on Benzo(a)Pyrene Induced ForestomachTumorigenesis in Murine Tumor Model System. Journal of Experimental & Clinical Cancer Research. (2005) 24 (4) 555-563. (IF): 1.2

11

Dhiman M, Malhotra N and Kale RK. Quercetin as a radiomodulator. Indian Journal of Radiation Research. (2004) 1(2): 18-19.

C. Book chapter

1

Gupta S,Dhiman M, Wen JJ, Garg NJ. ROS signaling of inflammatory cytokines during T. cruzi infection. Advances in Parasitology(2011) 76:153-70.

D. Presentations made at national and international conferences.

1

Dhiman M and Garg NJ. Role of NADPH-Oxidase derived reactive oxygen species in chronic myocardial pathology in mice infected by Trypanosomacruzi. 59th Annual Meeting ofAmerican Society of Tropical Medicine and Hygiene (ASTMH), Atlanta, Georgia. November 3-7, 2010

2

Dhiman M and Garg NJ. Role of NADPH Oxidase derived reactive oxygen species in progression of myocarditis during TrypanosomaCruzi Infection. National Postdoc Appreciation Week, symposium at UTMB, September 2010.

3

Dhiman M, Jasmine Pando, Estrada-Franco JG, Aguilar FR, Corzo SB, Perez GM, Sandoval RG, Garg NJ. Myeloperoxidase-Induced Oxidative/Nitrosative Stress in Human Chagasic Patients. 108th General Meeting, American Society for Microbiology, Boston, Massachusetts. June 2008.

4

Dhiman M and Garg NJ. Development of nitrosyl-plasma proteome in Chagas disease: Identification of novel diagnostic biomarkers. 14th Annual Meeting of Society for Free Radical Biology and Medicine, Washington DC. November 2007.

5

Dhiman M, Malhotra N and Kale RK. Radiomodulatory Effects of Quercetin in Murine Splenocytes. Biosparks, Annual Research Festival organized by School of Life Sciences, Jawaharlal Nehru University (JNU), New Delhi. February 2005.

Poster Presentations:

1

Valena C Martinez Sellers, Monisha Dhiman and Nisha Jain GargTesting the efficacy of (a) recombinant antigens for diagnosis of T. cruziinfection and (b) biomarkers of Chagas Disease. Evaluation of Metabolic and xidant/Inflammation Status of Human Chagasic Patients.Medical Student Summer Research Program (MSSRP), at UTMB, June 2011.

2

Yun A. Coronado, Monisha Dhiman, and Nisha J. Garg, Evaluation of Metabolic and Oxidant/Inflammation Status of Human Chagasic Patients. Medical Student Summer Research Program (MSSRP), at UTMB, June 2011.

3

Lozano-Garcia Jose, Dhiman M, and Garg NJ. Role of NADPH-oxidase dependent reactive oxygen species in Chagas disease. Medical Student Summer Research Program (MSSRP), poster presentation at UTMB, June 2010.

4

Dhiman M and Garg NJ. Activation of NADPH-Oxidase-reactive oxygen species-inflammatory cytokines pathway contribute to acute myocardial pathology in mice infected by Trypanosomacruzi. 16th Annual Pathology Department Trainee Research Day,University of Texas Medical Branch, Galveston, Texas, USA. May 2010.

5

Dhiman M and Garg NJ.Splenic activation of NADPH-Oxidase-reactive oxygen species-inflammatory cytokines pathway contribute to acute myocardial pathology in mice infected by Trypanosomacruzi.McLaughlin Colloquium 2010, University of Texas Medical Branch, Galveston, Texas, USA. April 2010.

6

Dhiman M and Garg NJ. Inhibition of NADPH-oxidase Attenuates T cruzi-induced Cardiac Pathology. “International Education Week” organized by PAHO/WHO Collaborating Center for Training in International Health at UTMB, Galveston. November, 2009.

7

Dhiman M and Garg NJ. NADPH oxidase-derived Reactive Oxygen Species Enhance the Pro-Inflammatory Response in Mice Infected by Trypanosomacruzi. 109th General Meeting, American Society for Microbiology, Philadelphia, May 2009.

8

Dhiman M,Nakayasu E.S., Hosakote Y.M., Reynolds B.K , Wen J.J, Almeida I C and Garg NJ. Enhanced nitrosative stress during Trypanosomacruzi infection causes nitrotyrosine modification of host proteins: Implications in Chagas disease.Boston University School of Medicine’s 3rd Symposium on “Oxidative Post-translational modifications in the cardiovascular system”. Boston. Oct 2008.

9

Dhiman M, Jasmine Pando, Estrada-Franco JG, Aguilar FR, Corzo SB, Perez GM, Sandoval RG, Garg NJ. Myeloperoxidase-Induced Oxidative/Nitrosative Stress in Human Chagasic Patients. 108th General Meeting, American Society for Microbiology, Boston, Massachusetts. June 2008.

10

Dhiman M, Jasmine Pando, Estrada-Franco JG, Aguilar FR, Corzo SB, Perez GM, Sandoval RG, Garg NJ. Increased Myeloperoxidase Activity and Protein Nitration are Indicators of Chronic Inflammation in Chagasic Patients. 58th Annual Meeting of the Steele conference on Diseases in Nature Transmissible to Man (DIN), at Moody Garden Hotel, Galveston, Tx. April 22-24 2008.

11

Dhiman M, Jasmine Pando, Estrada-Franco JG, Aguilar FR, Corzo SB, Perez GM, Sandoval RG, Garg NJ. Increased Myeloperoxidase Activity and Protein Nitration are Indicators of Chronic Inflammation in Chagasic Patients. McLaughlin Colloquium 2008, University of Texas Medical Branch, Galveston, Texas, USA. April 2008.

12

Dhiman M, Jasmine Pando, Estrada-Franco JG, Aguilar FR, Corzo SB, Perez GM, Sandoval RG, Garg NJ. Increased Myeloperoxidase Activity and Protein Nitration are Indicators of Chronic Inflammation in Chagasic Patients. Molecular Basis of Infectious Diseases (MBID) Retreat,Texas A&M Institute of Biosciences and Technology, Houston. March 2008.

13

Dhiman M, Jasmine Pando, Estrada-Franco JG, Aguilar FR, Corzo SB, Perez GM, Sandoval RG, Garg NJ. Myeloperoxidase Activation and Increased Protein Nitration Oxidation in Chagasic Patients. 14th Annual Meeting of Society for Free Radical Biology and Medicine, Washington DC. November 2007.

14

Dhiman M, Pando J, Estrada-Franco JG, Aguilar FR, Corzo SB, Perez GM, Sandoval RG, Garg NJ. Correlation of chronic inflammation and seropositivity in chagasic human serum. Summer Undergraduate Research Program Poster Presentation. 2007, University of Texas Medical Branch, Galveston, Texas, USA. August 2007.

15

Dhiman M and Garg NJ. Development of Nitrosyl-plasma proteome in Chagas disease: Identification of novel diagnostic biomarkers. McLaughlin Colloquium 2007, University of Texas Medical Branch, Galveston, Texas, USA. March 2007.

16

Dhiman M, Malhotra N and Kale RK. Quercetin as a radiomodulator. International Conference on Recent Trends in Radiation Biology organized by Bhabha Atomic Research Centre (BARC), Bombay. December 2004.

17

Dhiman M, Malhotra N and Kale RK.Radiation Response of Wild and Mutant Strains of Spirulinaplatensis. International Conference on Trends in Cellular and Molecular Biology organized by School of Life Sciences, Jawaharlal Nehru University (JNU), New Delhi. March 2003.

18

Dhiman M, Malhotra N and Kale RK.Effect of High Doses of Ionizing Radiation on Two Strains of Spirulinaplatensis. Biosparks, Annual Research Festival organized by School of Life Sciences, Jawaharlal Nehru University (JNU), New Delhi. February 2003.

19

Dhiman M, Malhotra N and Kale RK. The Radioresistance of Spirulinaplatensis. International Conference on Radiation Damage organized by Institute of Nuclear Medicine and Allied Sciences (INMAS) New Delhi. November 2002.

C. Area of Research and Research Perspectives

I have been working on oxidative stress, reactive oxygen species (ROS)/reactive nitrogen species (RNS), and inflammation and their role in various diseases for a decade now. Since last six (6) years I have been working on parasite pathology, inflammation and oxidative stress. I want to pursue my career in the field of oxidative stress and inflammation since it is a challenging area. I have two main focus of research.First, to understand the role of oxidative stress in instigation and/or sustenance of the pathological processes (inflammation, oxidative damage, and fibrosis) that contributes to disease severity. I have worked extensively on oxidative plasma proteome analysis by 2-dimensional gel electrophoresis/ LC-MS/MS and MALDI-TOF-MS/ Western blotting approach to identify disease-and disease-state specific biomarkers in Chagas Disease.Secondly, to see the infection-induced inflammatory responses that initiate a feedback cycle of mitochondrial decay, respiratory chain inefficiency, and increased oxidative stress, in this regard I have used variety of knockout and transgenic mice to compare the role of mitochondrial ROS and NADPH-oxidase dependent ROS in signaling inflammation and disease pathology. In addition I have also screened human chagasiccardiomyopathicpatient’splasma/ serum to investigate the diagnostic and prognostic efficacy of the markers of inflammation, oxidative stress and antioxidant status in identifying T. cruzi infection and Chagas disease severity.My focus of future research will be to know whether ROS/RNS induced oxidative stress activates innate defense response during carcinogenesis and what role does the antioxidants play in that regard. My ultimate goal is to delineate the complex interrelationships between the oxidative stress and inflammatory mediators, wherein the promise of antioxidant and anti-inflammatory therapies in controlling progressive disease conditions can be realized.

D. Past Research/Projects Completed
Research during post -doctoral fellowship

Trypanosomacruzi, a causative agent for Chagasiccardiomayopathy. Disease pathogenesis includes mitochondrial dysfunction and oxidative stress. In subsequent studies, we have found that treatment of T. cruzi-infected animals with an antioxidant and anti-parasite therapy (not the anti-parasite therapy alone) was effective in preventing the mitochondrial and cardiac oxidative pathology and preserving cardiac function. Based on these studies, we focused on murine model system and human sera samples to understand patho-physiology of Chagas disease. I have developed a chagasic plasma proteome with an aim to identify the differentially expressed/released and/or modified proteins that would be specific/sensitive markers of cardiac disease status and provide insights into the pathological mechanisms associated with Chagas disease development. Emphasis was laid on the empirical determination of various protein modifications such as protein carbonyl, 3-nitroTyr (3NT), and diTyr contents in the chagasic plasma samples compared to normal controls. In a second project I worked with chagasic human sera to see the correlation between the disease progression and inflammatory markers. I also used human sera to do some auto-immune related experiments as Chagas disease also shows some auto-immune disease like characteristics. My more recent project suggested that reactive oxygen species (ROS) is an important regulator of inflammatory cytokines in chagasic host. My inhibition studies with cultured and primary macrophages showed that NOX/ROS was a critical regulator of cytokine production in response to T. cruzi infection. In vivo studies using splenocytes of T. cruzi infected mice, with or without in vitro stimulation with parasite antigens, validated the above observations and demonstrated that inhibition of NOX by apocynin or DPI or use of ROS scavenger substantially inhibited the activation and proliferation of phagocytes and inflammatory mediators (IL-1, IL-6, IFN-?, and TNF-?). I have expanded my research towards identification of molecular and biochemical pathways that are perturbed and contribute to symptomatic progression of chronic Chagas disease. I utilized NADPH-oxidase, MnSOD and GPx knockout and transgenic mice to compare the role of mitochondrial ROS and NOX/ROS in signaling inflammation and disease pathology and severity. Results from these studies elucidate the role of ROS in mediating inflammatory responses and signaling cascades animal models with chagasic cardiomyopathy which may have important implications for the development of a therapy designed to protect the host against the infection and the pathology induced by T cruziinfections.

2. Summary of Ph.D. research: “CHEMICAL MODIFICATION OF RADIATION EFFECTS ON MURINE SPLENOCYTES”.

Radiation therapy is considered to be one of the most important and popular tools to cure cancer; the presence of hypoxic cells in tumors limits its success. To overcome this difficulty many efforts have been expended in search of agents, which either sensitize the cancer cells or protect the surrounding normal tissue. Although number of chemicals have been examined for their radioprotective ability but radio-modulator which are already being used in field of medicine need to be explored further and also the modulators of plant origin are of great interest for their antioxidant profile, non-toxic nature and ubiquitous presence. Keeping this in mind two chemicals were tested for their radio-modulatory properties in the present work Quercetinis a polyphenolic flavonoid and one of the major dietary flavonoid regularly being consumed by human beings and Chlorpromazine which is one of the most typical drugs that interact with PI signaling pathway. Chlorpromazine is phenothiazine cationic amphiphilic drug, interacts with membrane phospholipids, thereby reducing the PKC activity in the membrane fraction and block excitatory processes

Murine splenocytes isolated and cultured in RPMI medium were irradiated to various doses of gamma radiation (0-5Gy) with and without quercetin and chlorpromazine to assess the modulation of radiation induced oxidative damage at three levels namely: 1.Damage to membranes (studies done on lipid peroxidation, membrane fluidity, ATPase activity); 2. Impaired antioxidant defense system due to reactive oxygen species (ROS) generation (by estimating Glutathione-S-Transferase, Super-Oxide-Dismutase, DT-Diaphorase and Glyoxalase I enzyme activity); 3. DNA damage (by assessing the DNA fragmentation by spectrophotometric method, inter-nucleosomal fragment ladder formation, fluorescence microscopy and FACS analysis). In addition, two major damage indicators like Lactate Dehydrogenase (LDH) activity and nitric oxide levels were also estimated. An attempt was made to evaluate the radio-modifying potential of Quercetin and Chlorpromazine and their wide acceptability at clinical level by using various biological end points

3. Summary of M. Phil research: “THE RADIO-RESISTANCE OF SPIRULINA PLATENSIS”.

Stress in any environmental factor potentially unfavorable to living organisms including alteration in their metabolic or physiological activity. In present work gamma radiation was used as stress to the alkaliophilic cyanobacteria Spirulinaplatensisand one of its vandate resistant mutants. The wild and mutant types of culture of Spirulina were irradiated and studied for important biological parameters including the protein content, pigment content (chlorophyll a, phycocyanin and phycoerythrin), ß carotene content, lipid peroxidation, nitric oxide levels and phosphatase activity. This study indicated that the radio-resistant nature of Spirulina was due to presence of high levels of antioxidant, which are not affected by the high or very high doses of gamma radiation. The cell survival studies revealed that the vandate resistant mutant was more resistant to radiation then the wild type as it was not adversely affected rather changes in cellular machinery in response to vandate helped Spirulina in combating radiation stress.

4. Summary of M. Sc. Project: “Effect of gamma radiation on the chick spinal cord”.

The study involved the investigation of the effect of gamma radiation on the various chick tissues importantly the spinal cord, which is considered to be the most resistant tissue of the central nervous system (CNS). The studies included the wax embedded sectioning to observe the histopathological changes in the spinal cord after gamma irradiation.

5. Other research work carried out:

1

Trained first yearstudent of Clinical Laboratory Sciences, Cecilia Krystyne Vallejo of UTMB under summer Research Program , April-May 2012

2

Trained first year medical student Valena C Martinez Sellersof UTMB under Medical Student Summer Research Program (MSSRP), May-June 2011

3

Trained first year medical student Yun A. Coronadoof UTMB under Medical Student Summer Research Program (MSSRP), May-June 2011

4

Trained first year medical student Juan J Vizcaino of UTMB under T35 Training Program, May-July, 2009.

5

Guided and work planned for a undergraduate student Jasmine Pandofrom New Mexico State University, Las Cruces, NM, under Summer Undergraduate Research Program at University of Texas Medical Branch, Galveston, Tx.June-August, 2007.

6

Planned and guided two students for their M Sc. projects under supervision of Prof. R.K. Kale.

“Influence of Divalent Cations on the Radiation Induced Oxidative Stress” for Mr. Vijay Kumar, School of Life Sciences, Jawaharlal Nehru University (JNU), New Delhi. December, 2003 - April, 2004.

"Modulation of Radiation Induced Oxidative Stress with Quercetin” for Mr. BheemRatnaRawat, School of Life Sciences, Jawaharlal Nehru University (JNU), New Delhi. December, 2003 - April, 2004.