K. Sandeep Prabhu, PhD
- Ph.D., Biochemistry, VMSRF-University of Mysore , India
- M.Sc., Biochemistry, University of Mysore , India
- B.Sc., Biochemistry, Botany & Zoology, University of Mysore , India
Emily Finch, BS (Graduate Student- Immunology/Infectious Disease and CTSI Scholar)
Hunter Fraker Undergrad Student (Schreyer Honors College)
James Frisbie, Undergrad Student (Schreyer Honors College)
Dr. Avinash Kudva, PhD (Post-doctoral Research Scholar)
Chang Liao, MS (Graduate Student- Pathobiology)
Erica Mellinger, Undergraduate Student (Schreyer Honors College)
Dr. K. Sandeep Prabhu, PhD (Principal Investigator; Professor)
Ashley Shay, BS (Graduate Student- Molecular Medicine and NIH T32 Trainee)
Jocelyn Stoudt, Undergraduate Student (Schreyer Honors College)
Dr. Vivek Narayan, PhD (Graduate Student), Post-doctoral Scholar, MGH-Harvard Medical School and Boston Children's Hospital.
Dr. Naveen Kaushal, PhD (Post-doctoral Research Scholar), Assistant Professor, Department of Biophysics, Panjab University, Chandigarh, India.
Nicole Wilski, (Undergrad Student): Graduate Student; Thomas Jefferson University - Microbiology & Immunology ProgramDr. Shakira Nelson (Graduate Student- Pathobiology), CPFP Post-doctoral Fellow, NCI, Bethesda, MD
Sara Farwell (BS Student), Graduate Student, Lehigh University
Steven Cornelius (BS Honors Student); MD Student, Penn State Hershey College of Medicine
Kayleigh McCormick (BS Honors Student); DVM Student, UPENN
Dr. Ujjawal H. Gandhi, M.B.,B.S. PhD (PhD Molecular Toxicology): Chief Medical Resident, NYU
Dr. Tejo Nagaraja, PhD (Professor, Thapar University, India) DBT-CREST Visting Professor
Dr. Uma Palempalli (Associate Professor, SV University for Women, Tirupati, India) DBT-CREST Visiting Professor
Dr. Ravindra C. Kodihalli (Post-doctoral Scholar) MIT, Cambridge
Dr. Anil Kotha, PhD (Post-doctoral Scholar) UT San Antonio, TX
Kelsey Hafer (BS Schreyer's Honors Student); DVM Student, U Penn
Amanda Tuchinsky (BS Schreyer's Honors Student); MD Student, Jefferson Med School
Pranav Maddali, BS (Research Tech); PhD Student; RPI- Albany, NY
Dr. Christopher Chiaro, PhD (Post-doctoral Research Scholar)
Dr. Ryan J. Arner, PhD (Research Associate)-DETRA-PSU Program Staff
Dr. Parisa Kalantari (Post-doc) Currently Post-doc @ UMass, Worcester
Pradeep Bodumalla (MS-Pathobiology)
Dr. Hema Vunta (PhD-Pathobiology) Currently- Lecturer, College of Pharmacy, Cincinnati, OH
Dr. K. Muralidhar (Visiting Professor)- Professor of Zoology, University of Delhi, India
Dr. Uma Palempalli (Visiting Professor)- Professor of Microbiology, Tirupati, India
Stephanie Larson (MS- Pathobiology) Currently DO Student-Lake Erie College of Osteopathic Medicine
Jessica Stahle (BS- Honors) Currently- DVM Student at U Penn
Deepa Bhat (BS Honors) Currently- Scientist, FBI
Katie Miro (BS Honors) Currently MD student; Temple
VB SC 514 (NUTRN 514) Prostaglandins and Leukotrienes (Alternate Sp semester)
The course provides an in-depth coverage of how fatty acids are metabolized in eukaryotes by various enzymatic and non-enzymatic mechanisms. The course will emphasize on the physiological roles of these fatty acid oxidation products in general health, inflammation, and reproduction along with their cellular basis of action via receptor-dependent and -independent mechanisms. (3 Credits)
VB SC 451 Immunotoxicology of Drugs and Chemicals (Coordinator: Dr. Prabhu/Co-instructor: Dr. Na Xiong) (Fa semester)
The immunotoxicology course will focus primarily on the effects of environmental chemicals, therapeutics, and recreational drugs on the immune system. Immunomodulatory mechanisms will be examined at systemic, cellular and molecular levels. Discussions will include theory, principles, and methodology and key issues in immunotoxicology. (3 Credits)
VB SC 330 Introduction to Molecular Pharmacology (Coordinator: Dr. Adam Glick/Co-instructor: Dr. Prabhu) (Sp Semester)
Molecular interactions between drugs and their tissue receptors and possible modifications of drugs to target different receptors will be discussed. Drugs used to treat infectious disease, cardiovascular disease, immune modulators, and anti-cancer drugs will be examined for their molecular interactions. Students will understand the complexities of new drug design and development from the initial stages of laboratory development to final approval for use by the Food and Drug Administration. (3 Credits)
There are five current projects in the lab:
1. Effect of selenium on leukemia stem cells
2. Targeting leukemia using novel lipid mediators derived from omega-3 fatty acids
3. Effect of selenium on gut inflammation
4. Effect of host selenoproteins in helminth infection models
5. The role of selenoproteins in the transcription of HIV-1
Regulation of pro-inflammatory gene expression by oxidative stress-dependent mechanisms and the role of selenium in macrophages
Respiratory burst and the reactions of the electron transport system in mitochondria have the ability to produce a variety of oxygen and nitrogen radicals, commonly called reactive oxygen (ROS) or nitrogen (RNS) species by different mechanisms. Although these ROS/RNS play an important role in the defense of the host, increased production of these radicals is thought to be one of the major mechanisms accompanying inflammation, as seen in atherosclerosis, cancer, asthma, Alzheimer's disease and arthritis. It is increasingly recognized that many cellular signaling pathways are oxidation-sensitive, and that ROS may provide a common link between proinflammatory pathways and pathologies. Extensive evidence from many laboratories, including ours, indicates that ROS can regulate gene expression by modulating a large number of redox-sensitive transcription factors. Therefore, the antioxidant capacity of immune cells (e.g., macrophages) is very important to maintain optimal overall redox or oxidative tone. This is accomplished by a multi-tier system in which selenium (Se) in the form of Se-glutathione peroxidases, thioredoxin reductases, and other selenoproteins. However, the exact mechanism of antioxidant protection by Se is still unclear.
Current projects in this area:
1) The regulation of cyclooxygenase-2 (COX-2), a prototypical proinflammatory gene, by Se. We are trying to understand how Se abrogates the endotoxin- and cytokine-mediated COX-2 expression by interfering with the activation of the redox-sensitive transcription factor, nuclear factor-kappa B (NF-kB). These studies are mainly performed in bone marrow-derived macrophages from mice that are maintained on a Se-deficient and Se-supplemented diets.
2) Statins are drugs used in the treatment of hypercholesterolemia and these have been hypothesized to decrease the expression of selenoproteins, which might explain some of the side-effects (like myopathy, rhabdomyolysis, and depression) of these promising drugs. We are trying to understand the role of Se in alleviating these side effects, the molecular effects that are commonly seen in in-vitro culture systems, and whether these changes have a “signature pattern” like those observed during Se deficiency.
3) Increased oxidative stress leads to increased activation of NF-kB, which can modulate several transcription factors by a mechanism known as “transcription factor squelching”. Using proteomic and genetic approaches, we are making an attempt to identify these NF-kB interacting proteins. One such example is the interaction of p65 subunit with peroxisome proliferator-activated receptor- a and its role on the expression of apolipoprotein A-I (apoA-I) in the hepatocytes.
4) The role of selenium in HIV/AIDS: There is epidemiological data indicating the beneficial role of selenium in HIV/AIDS. We are trying to understand the mechanism of action of selenium in HIV/AIDS via different mechanisms. Our data suggests that selenoproteins are critical regulators of proviral transcription.
Through these studies, we hope to gain understanding of the anti-oxidant property of Se and its role as a therapeutic agent in human and animal health.
Isolation and characterization of endogenous ligands for the peroxisome proliferator-activated receptors (PPARs)
The PPARs have enjoyed the spotlight for many reasons. These transcription factors are ligand-inducible nuclear receptors that modulate gene expression in response to a broad spectrum of compounds. The recognition that PPARs are indeed nuclear receptors for polyunsaturated fatty acids, some eicosanoids and also lipid-lowering and antidiabetic drugs, has opened many exciting avenues of research and drug discovery. Recent studies on the PPAR function have extended the role of these transcription factors beyond energy homeostasis to master gene in adipogenesis and also determinants in inflammation control. Using our expertise in the large-scale synthesis of oxidized lipids, we are involved in a collaborative project with the Molecular Toxicology Group in the Department to evaluate some of the promising compounds as ligands for nuclear receptors, including PPARs.
Targeting of leukemia stem cells: In collaboration with Dr. Robert Paulson
Please see the video:
N. Kaushal, A. K. Kudva, A. D. Patterson, C. Chiaro, M. J. Kennett, D. Desai, S. Amin, B. A. Carlson, M. T. Cantorna, and K. S. Prabhu (2014) Crucial role of macrophage selenoproteins in experimental colitis. J. Immunol. (E-ahead of print)
K. C. Nicolaou, P. Heretsch, A. ElMarrouni, C. R. Hale, K. K. Pulukuri, A. K. Kudva, V. Narayan, K. S. Prabhu (2014) Total synthesis of D12-prostaglandin J3- a highly potent and selective anti-leukemic agent. Angew. Chem. Aug 5. doi: 10.1002/anie.201404917. (Epub ahead of print)
U.H. Gandhi, N. Kaushal, S. Hegde, E. Finch, A.K. Kudva, M.J. Kennett, C. T. Jordan, R. F. Paulson, K. S. Prabhu (2014) Role of endogenous eicosanoids in the suppression of leukemia by selenium. Cancer Res. (In Press)
M. Vijay Kumar, K. S. Prabhu, C. J. Rogers (2014) The Microbiome and Obesity?An Established Risk for Certain Types of Cancer. The Cancer Journal (Accepted; in Press)
2013:Kudva, N. Kaushal, S. Mohinta, M. J. Kennett, A. August, R. F. Paulson, and K. S. Prabhu (2013) Stability, bioavailability, and hypersensitivity of omega-3 derived anti-leukemic D12-PGJ3. PLoS One Dec 2;8(12) e80622
U. H. Gandhi, T. P. Nagaraja, and K. S. Prabhu (2013) Selenoproteins and their role in oxidative stress and inflammation. Curr. Chem. Biol. 7; 1-9
Y-C. Chen, K. S. Prabhu, A. Mastro (2013) Is selenium a potential treatment for cancer metastasis? Nutrients 5; 1149-68.
Y-C. Chen, K. S. Prabhu*, A. Mastro* (2013) Dietary selenium supplementation modifies breast tumor growth and metastasis. Int. J. Cancer 133;2054-64.
M.R. Flock, C. J. Rogers, K. S. Prabhu, P. M. Kris-Etherton (2013) Immunometabolic role of long-chain omega-3 fatty acids in obesity-induced inflammation. Diabetes Metab. Res. Rev. 29; 431-45.
Kaushal N, Narayan V, Gandhi UH, Nelson SM, Kotha AK and Prabhu KS (2012). Inflammation, oxidative stress, and antioxidants. In “Chronic Inflammation: Nutritional & Therapeutic interventions”. Eds. S. Roy, D. Bagchi, and S. P. Raychaudhuri. CRC Press (New York); Chapter 19, pp 259-273.
B. Belda, J. T. Thompson, R. Sinha, K. S. Prabhu, and J. P. Vanden Heuvel (2012) The dietary fatty acid 10E12Z-CLA induces epiregulin expression through COX-2 dependent PGF2a synthesis in adipocytes. Prostaglandins Other Lipid Mediat. [E-Pub ahead of print May 11, 2012].
Ravindra KC, Narayan V, Lushington GH, Peterson BR, Prabhu KS. Targeting of Histone Acetyltransferase p300 by Cyclopentenone Prostaglandin Δ(12)-PGJ(2) through Covalent Binding to Cys(1438).Chem Res Toxicol. 2012 Feb 20;25(2):337-47.
Kaushal N, Gandhi UH, Nelson SM, Narayan V and Prabhu KS (2011). Selenium and Inflammation. In Selenium: Its Molecular Biology and Role in Human Health (2012) 3rd Edition. Springer Publications. Chapter 35, pp 443-456.
Hegde S, Kaushal N, Ravindra KC, Chiaro C, Hafer KT, Gandhi UH, Thompson JT, Vanden Heuvel JP, Kennett MJ, Hankey P, Paulson RF, Prabhu KS. Delta12-prostaglandin J3, an omega-3 fatty acid-derived metabolite, selectively ablates leukemia stem cells in mice. Blood. 2011 Oct 3. [Epub ahead of print] PMID: 21967980 (Ney, P: News and Views, Blood, Dec 22, 2011)UH Gandhi, N Kaushal, KC Ravindra, S Hegde, SM Nelson, V Narayan, H Vunta, RF Paulson, KS Prabhu (2011) Selenoprotein-dependent Up-regulation of Hematopoietic Prostaglandin D2 Synthase in Macrophages Is Mediated through the Activation of Peroxisome Proliferator-activated Receptor (PPAR)g. J. Biol. Chem. 286:27471-82.
S. Nelson, X. Lei, and K. S. Prabhu (2011) Selenium status regulates the expression of alternative activation markers in macrophages. J. Nutr. [E-Pub ahead of print]
N. Kaushal, S. Hegde, R. F. Paulson, and K. S. Prabhu (2011) The regulation of erythropoiesis by selenium. Antiox. Redox Signal. 14:1403-12.
M. Ray, S Yu, C. B. Wilson, N. Kaushal, K. S. Prabhu, and P. Hankey (2011) Regulation of TLR4 signaling in macrophages by the Ron receptor tyrosine kinase and its ligand, MSP. J. Immunol. 185:7309-16.
V. Narayan, K.C. Ravindra, C. Chiaro, D. Carey, B. B. Aggarwal, A. J. Henderson, and K. S. Prabhu (2011) Celastrol inhibits tat-dependent human immunodeficiency virus (HIV) transcription and replication. J. Mol. Biol. 410(5):972-83.
D. Desai, N. Kaushal, R. J. Arner, U. H. Gandhi, C. D’Souza, K. El-Bayoumy, S. G. Amin, and K. S. Prabhu (2010) Evaluation of the anti-inflammatory properties of selenium-derivatives of celecoxib. Chem. Biol. Interact. 188:446-56.
Y-C Chen, D. Sosnoski, U. H. Gandhi, L. Novinger, K. S. Prabhu*, and A. M. Mastro* (2009 Selenium modifies the osteoblast inflammatory stress response to bone metastatic breast cancer. Carcinogenesis. 30(11):1941-8 (*Corresponding authors)
D Jiang, C. Chiaro, P. Maddali, K.S. Prabhu, and D. G. Peterson (2009) Identification of hydroxycinnamic acid –maillard reaction products in low-moisture baking model systems. J. Agric. Food Chem. 57: 9932-43
Kalantari P, Narayan V, Henderson AJ, and Prabhu KS (2009) 15-deoxy-PGJ2 inhibits HIV-1 transactivating protein, Tat, through covalent modification. FASEB J. March 19
Stahle JA, Vunta H, Reddy CC, and Prabhu KS (2009) Regulation of expression of apolipoprotein A-I by selenium status in hepatocytes. Eur. J. Nutr. March 18
Palempalli UD, Gandhi U, Kalantari P, Vunta H, Arner RJ, Narayan V, Ravindran A, and Prabhu KS (2009). Gambogic acid covalently modifies IkB-kinase-b subunit to mediate suppression of lipopolysaccharide-induced activation of NF-kB in macrophages. Biochem. J. 419 (2): 401-409.
DeKeyser JG, Stagliano MC, Auerbach SS, Prabhu KS, Jones AD, and Omiecinski CJ (2009) Di(2-ehtylhexyl)phthalate is a highly potent agonist for the human constitutive androstane receptor splice variant, CAR2. Mol. Pharmacol. Feb 11
Hendricks III GL, Hadley JA, Krzysik-Walker SM, Prabhu KS, Vasilatos-Younken R, Ramachandran R (2009) Unique profile of chicken adiponectin, a predominantly heavy molecular weight multimer, and relationship to visceral adiposity. Endocrinology. March 19
Desai A, Konda VR, Darland G, Austin M, Prabhu KS, Bland J, Caroll B, and Tripp ML (2009) META060 inhibits multiple kinases in the NF-kB pathway and suppresses LPS-mediated inflammation in-vitro and in-vivo. Inflamm. Res. January
Kalantari P, Narayan V, Natarajan SK, Muralidhar K, Gandhi UH, Vunta H, Henderson AJ, Prabhu KS. Thioredoxin reductase-1 negatively regulates HIV-1 transactivating protein Tat-dependent transcription in human macrophages. J Biol Chem. 2008 Oct 3. [Epub ahead of print] PMID: 18835810 [PubMed - as supplied by publisher]
Vunta H, Belda BJ, Arner RJ, Channa Reddy C, Vanden Heuvel JP, Sandeep Prabhu K. Selenium attenuates pro-inflammatory gene expression in macrophages. Mol Nutr Food Res. 2008 May 15. [Epub ahead of print] PMID: 18481333 [PubMed - as supplied by publisher]
Chiaro CR, Morales JL, Prabhu KS, Perdew GH. Leukotriene A4 metabolites are endogenous ligands for the Ah receptor.Biochemistry. 2008 Aug 12;47(32):8445-55. Epub 2008 Jul 11. PMID: 18616291 [PubMed - indexed for MEDLINE]
NIH (NIDDK, NCI, NCCAM), AICR, Campbell Foundation, and College of Ag Sci, Penn State Cancer Institute, Penn State University
American Institute for Cancer Research, Washington, D.C.
International Symposium on host-pathogen interactions, University of Hyderabad and National Institute of Animal Biotechnology, Hyderabad, India.
International Trace Element Society's Trace Elements in Man and Animals (TEMA)-15 meeting, Orlando, FL
Experimental Biology (American Soc of Nutrition), Boston
International Symposium on Bioactive Lipids in Cancer, Inflammation, and Other Related Diseases, San Yuan, Puerto Rico (Travel award for Dr. Avinash Kudva from NIEHS/NIH; Travel Award for Emily Finch from Clinical Translational Sciences Institute, Penn State)
International Symposium on Selenium in Biology and Medicine, Berlin, Germany
Experimental Biology, San Diego, CA
AICR, Washington, D.C.
Experimental Biology, Washington, D. C.
Eicosanoid Research Foundation, Seattle, WA
Trace Element Society Meeting, TEMA-14, Enshi, China
AICR Meeting, Washington, D. C.
Experimental Biology 2010, Anaheim, CA- Shakira Nelson, Recipient of the ASBMB Graduate Travel Award
Graduate Exhibition, Penn State University
International Symposium on Selenium in Biology and Medicine- Kyoto, Japan
FASEB Summer Research Conference- Snowmass Village, Colorado
AICR Food, Nutrition, and Cancer Conference, Washington, D.C.
Experimental Biology 2009 (Recipients of the ASBMB Graduate Student Travel Awards: Ujjawal Gandhi and Vivek Narayan)
Eicosanoid Research Foundation 2009 (Cancun, Mexico)
Lab Flow Appointments (Please consult with Dr. Prabhu for permission):
- Immunology and Infectious Disease Research Faculty
Regulation of immune function by oxidative stress and antioxidants, including selenium. Regulation of HIV transcription by selenium.
- Molecular Toxicology & Carcinogenesis Research Faculty
Regulation of immune function by oxidative stress and antioxidants, including selenium. Regulation of HIV transcription by selenium.