Exposure to environmental and therapeutic pro-oxidative stressors generate a class of potent lipid mediator, Platelet-activating factor (PAF), and PAF-like agonists as a bystander effect. These PAF lipids activate a widely-expressed G-protein coupled, PAF-receptor (PAFR) to modulate local pro-tumoral and systemic immune responses. The major research interests of my laboratory are:
- Determining the mechanisms of pro-oxidative stressors in impacting cancer growth and efficacy of therapeutic agents.
- Evaluating the rationale combination approaches to target the PAFR pathway with the goal of enhancing the efficacy of therapeutic agents.
- Exploring the translational relevance of the PAFR pathway in mediating environmental pollutants and chemical carcinogen-induced responses.
- Defining the functional significance and mechanisms of microvesicle particles (MVP) release in response to therapeutic agents, environmental pollutants, and chemical carcinogens.
We explore molecular biology, immunology, and pharmacological approaches, including microvesicle particles analysis, gene deletion/overexpression, gene array, qPCR, western blotting, and flow cytometry with multiple novel cellular systems, relevant mouse models including genetic knockout and transgenic, as well as human samples for our research. Our basic and translational research projects involve collaborations with colleagues, including Physician-Scientists and Pathologists, and primarily use melanoma, lung, and pancreatic cancer models. My laboratory has been funded by grants, including from various Foundations and the NIH.
American Association for Cancer Research
American Society for Pharmacology and Experimental Therapeutics
American Cancer Society Cancer Action Network
Society for Investigative Dermatology
PTX7021-01: ESW I (Cancer Pharmacology & Therapeutics)
PTX7022-01: ESW II (Cancer Pharmacology & Therapeutics)
PTX7011: Thesis Development Workshop
PTX8014: Integrative Pharmacology and Toxicology Methods
PTH816: Overview of Animal Research
- Institutional Animal Care and Use Committee (IACUC; 2015 - Present), Wright State University (WSU)
- Institutional Biosafety Committee (IBC; 2015 - Present), WSU
- Admissions Committee (2015 - Present), WSU Dept of Pharmacology & Toxicology
- Scholarship Committee (2015 - 2019), WSU Dept of Pharmacology & Toxicology
- Faculty Retreat Committee (2016 - 2017), WSU Dept of Pharmacology & Toxicology
- Torralba EJV, Singh S, Short RF, Rapp CM, Henkels KH, Sahu RP, Travers JB. Radiation Therapy Produces Microvesicle Particle Release in HaCaT Keratinocytes. Skin Research & Technology 2023; 29(5):e13332.
- Thyagarajan A, Rapp CM, Schneider L, Lund A, Travers JB, Sahu RP. Exposure to diesel exhaust particulates and desert sand dust generates microvesicle particles and platelet-activating factor agonists. Skin Research & Technology Journal 2023; 29(4):e13312
- Abunada A, Sirhan Z, Thyagarajan A, Sahu RP. Tyrosine Kinase Inhibitors and human epidermal growth factor receptor-2 positive breast cancer. World J of Clinical Oncology 2023; 14(5): 198-202.
- Pathipaka R, Thyagarajan A, Sahu RP*. Melatonin as a drug repurposing for melanoma treatment. Medical Sciences 2023;11(1):9.
- Thyagarajan A, Awasthi K$, Rapp CM, Johnson RM, Chen Y, Miller KLR, Travers JB, Sahu RP. Topical application of gemcitabine generates microvesicle particles in human and murine skin. BioFactors, 2022; 48(6):1295-1304.
- Effects of miRNA-149-5p and Platelet-Activating Factor-Receptor Signaling on the Growth and Target Therapy Response on Lung Cancer Cells. Int J Mol Sci. 2022; 23(12):6772.
- Sirhan Z, Thyagarajan A, Sahu RP. The efficacy of tucatinib-based therapeutic approaches for HER2-positive breast cancer. Mil Med Res. 2022; 9(1):39.
- Liu L, Awoyemi AA, Fahy KE, Thapa P, Borchers C, Wu BY, McGlone CL, Schmeusser B, Sattouf Z, Rohan CA, Williams AR, Cates EE, Knisely C, Kelly LE, Bihl JC, Cool DR, Sahu RP, Wang J, Chen Y, Rapp CM, Kemp MG, Johnson RM, Travers JB. Keratinocyte-derived microvesicle particles mediate ultraviolet B radiation-induced systemic immunosuppression. J Clin Invest. 2021,131(10):e144963.
- Borchers C, Thyagarajan A, Rapp CM, Travers JB, Sahu RP. Evaluation of SARS-CoV-2 Spike S1 Protein Response on PI3K-Mediated IL-8 Release. Med Sci (Basel). 2021,9(2):30.
- Travers JB, Rohan JG, Sahu RP. New Insights Into the Pathologic Roles of the Platelet-Activating Factor System. Front Endocrinol. 2021,12:624132.
- Mallipeddi H, Thyagarajan A, Sahu RP. Implications of Withaferin-A for triple-negative breast cancer chemoprevention. Biomed Pharmacother. 2021,134:111124.
- Chauhan SJ, Thyagarajan A, Chen Y, Travers JB, Sahu RP. Platelet-Activating Factor-Receptor Signaling Mediates Targeted Therapies-Induced Microvesicle Particles Release in Lung Cancer Cells. Int J Mol Sci. 2020, 12(22): 8517.
- Konger RL, Ren L, Sahu RP, Derr-Yellin E, Kim YL. Evidence for a non-stochastic two-field hypothesis for persistent skin cancer risk. Scientific Reports. 2020,10(1):19200.
- Chauhan SJ, Thyagarajan A, Sahu RP. Functional significance of miRNA-149 in lung cancer: Can it be utilized as a potential biomarker or a therapeutic target? Austin J Med Oncol. 2020, 7(1): id1048.
- Thyagarajan A, Forino AS, Konger RL, Sahu RP. Dietary Polyphenols in Cancer Chemoprevention: Implications in Pancreatic Cancer. Antioxidants (Basel). 2020, 9(8): E651.
- Khader S, Thyagarajan A, Sahu RP*. Exploring signaling pathways and pancreatic cancer treatment approaches using genetic models. Mini Rev Med Chem. 2019, 19(14):1112-1125.
- Thyagarajan A, Kadam SM, Liu L, Kelly LE, Rapp CM, Chen Y, Sahu RP. Gemcitabine Induces Microvesicle Particle Release in a Platelet-Activating Factor-Receptor-Dependent Manner via Modulation of the MAPK Pathway in Pancreatic Cancer Cells. Int J Mol Sci. 2019, 20(1). pii: E32.
- Thyagarajan A, Alshehri MSA, Miller KLR, Sherwin CM, Travers JB, Sahu RP. Myeloid-Derived Suppressor Cells and Pancreatic Cancer: Implications in Novel Therapeutic Approaches. Cancers (Basel). 2019;11(11). pii:E1627.
- Abhilasha KV, Sumanth MS, Chaithra VH, Jacob SP, Thyagarajan A, Sahu RP, Rajaiah R, Prabhu KS, Kemparaju K, Travers JB, Chen CH, Marathe GK. p38 MAP-kinase inhibitor protects against platelet-activating factor-induced death in mice. Free Radic Biol Med. 2019;143:275-287.
- Sahu RP. Deciphering Mechanisms of UVR-Induced Tumoral Immune Checkpoint Regulation against Melanoma. Cancer Res. 2019;79(11):2805-2807.
- Konger RL, Derr-Yellin E, Ermatov N, Ren L, Sahu RP. The PPARg Agonist Suppresses Syngeneic Mouse SCC (Squamous Cell Carcinoma) Tumor Growth through an Immune-Mediated Mechanism. Molecules. 2019, 24(11). pii: E2192.
- Thyagarajan A, Shaban A, Sahu RP. MicroRNA-Directed Cancer Therapies: Implications in Melanoma Intervention. J Pharmacol Exp Ther. 2018, 364(1):1-12.
- Romer E, Thyagarajan A, Krishnamurthy S, Rapp CM, Liu L, Fahy K, Awotemi A, Sahu RP. Systemic Platelet-Activating Factor-Receptor Agonism Enhances Non-Melanoma Skin Cancer Growth. Int J Mol Sci. 2018;19(10). pii:E3109.
- Ocana JA, Romer E, Sahu RP, Pawelzik SC, FitzGerald GA, Kaplan MH, Travers JB. Platelet-Activating Factor-Induced Reduction in Contact Hypersensitivity Responses Is Mediated by Mast Cells via Cyclooxygenase-2-Dependent Mechanisms. J Immunol. 2018, 200(12):4004-4011.
- Harrison KA, Romer E, Weyerbacher J, Ocana JA, Sahu RP, Murphy RC, Kelly LE, Smith TA, Rapp CM, Borchers C, Cool DR, Li G, Simman R, Travers JB. Enhanced Platelet-Activating Factor Synthesis Facilitates Acute and Delayed Effects of Ethanol-Intoxicated Thermal Burn Injury. J Invest Dermatol. 2018, 138(11):2461-2469.
- Thyagarajan A, Sahu RP. Potential contributions of antioxidants to cancer therapy: Immunomodulation and Radiosensitization. Integrative Cancer Therapy. 2018, 17(2):210-216.
- Konger RL, Derr-Yellin E, Travers JB, Ocana JA, Sahu RP. Epidermal PPARγ influences subcutaneous tumor growth and acts through TNF-α to regulate contact hypersensitivity and the acute photoresponse. Oncotarget. 2017, 8(58):98184-98199.
- Thyagarajan A, Saylae J, Sahu RP. Acetylsalicylic acid inhibits the growth of melanoma tumors via SOX2-dependent-PAF-R-independent signaling pathways. Oncotarget. 2017, 8(30):49959-49972.
- Marasini B, Sahu RP. Natural anti-cancer agents: Implications in Gemcitabine-resistant pancreatic cancer treatment. Mini Reviews in Medicinal Chemistry. 2017, 17(11):920-927.
- Sahu RP, Harrison KA, Weyerbacher J, Murphy RC, Konger RL, Garrett JE, Chin-Sinex HJ, Johnston II ME, Dynlacht JR, Mendonca M, McMullen K, Li G, Spandau DF, Travers JB. Radiation therapy generates Platelet-activating Factor agonists. Oncotarget. 2016, 7(15):20788-800.
- Sahu RP. Expression of the platelet-activating factor receptor enhances benzyl isothiocyanate-induced apoptosis in murine and human melanoma cells. Molecular Medicine Reports. 2015; 12:394-400.
- Sahu RP, Ferracini M, Travers JB. Systemic chemotherapy is modulated by platelet-activating factor agonists. Mediators of Inflammation. 2015; 2015:820543.
- Ferracini M, Sahu RP, Harrison KA, Waeiss RA, Murphy RC, Jancar S, Konger RL, Travers JB. Topical photodynamic therapy induces systemic immunosuppression via generation of platelet-activating factor receptor ligands. Journal of Investigative Dermatology. 2015; 135(1):321-3.
- Sahu RP, Ocana JA, Harrison KA, Touloukian CE, Al-Hassani M, Sun L, Loesch M, Murphy RC, Althouse SK, Perkins SM, Speicher PJ, Tyler DS, Konger RL, Travers JB. Chemotherapeutic agents subvert tumor immunity by generating agonists of platelet-activating factor. Cancer Research. 2014; 74(23):7069-78.
- Sahu RP, Konger RL, Travers JB. Platelet-activating factor receptor agonists in tumor immunity. JSM Cell & Developmental Biology. 2014; 2(1): 1008.
- Sahu RP, Rezania S, Ocana JA, DaSilva-Arnold SC, Bradish JR, Richey JD, Warren SJ, Rashid B, Travers JB, Konger RL. Topical application of a platelet-activating factor receptor agonist suppresses phorbol ester-induced acute and chronic inflammation and has cancer chemopreventive activity in mouse skin: Potential role of mast cells. Plos One. 2014; 9(11):e111608.
- Hackler PC, Resus S, Konger RL, Travers JB, Sahu RP. Systemic Platelet-activating factor receptor agonists modulate Lung tumor growth and metastasis. Cancer Growth and Metastasis. 2014; 7: 27-32.
- Sahu RP, Irina Petrache, Matthew J. Turner, Badri M. Rashid, Raymond L. Konger and Jeffrey B. Travers. Cigarette smoke exposure results in systemic immunosuppression through the generation of platelet-activating factor agonists. Journal of Immunology. 2013; 190 (5): 2247-54.
- Lakhter AJ, Sahu RP, Sun Y, Kaufmann WK, Androphy EJ, Travers JB, Naidu SR. Chloroquine Promotes Apoptosis in Melanoma Cells by Inhibiting BH3 Domain-Mediated PUMA Degradation. Journal of Investigative Dermatology. 2013; 133(9): 2247-54.
- Konger RL, Xu Z, Sahu RP, Rashid BM, Mehta SR, Mohamed DR, DaSilva-Arnold SC, Bradish JR, Warren SJ, Kim YL. Spatiotemporal assessments of dermal hyperemia enable accurate prediction of experimental cutaneous carcinogenesis as well as chemopreventive activity. Cancer Research. 2012; 73(1):150-9.
- Sahu RP, Turner MJ, DaSilva SC, Rashid BM, Ocana JA, Perkins SM, Konger RL, Touloukian CE, Kaplan MH, Travers JB. The environmental stressor ultraviolet B radiation inhibits murine anti-tumor immunity through its ability to generate Platelet-activating factor agonists. Carcinogenesis. 2012; 33:1360-7.
- Sahu RP, DaSilva SC, Rashid B, Martel KC, Rezania S, Jernigan D, Bradish JR, Armstrong AB, Warren S, Konger RL. Mice lacking epidermal PPARγ exhibit a marked augmentation in photocarcinogenesis associated with increased UVB-induced apoptosis, inflammation and barrier dysfunction. International Journal of Cancer. 2012; 131: E1055-1066.
- Sahu RP, Kozman A, Yao Y, DaSilva SC, Rezania S, Martel KC, Warren S, Travers JB, Konger RL. Loss of the Platelet Activating Factor Receptor in mice augments PMA-induced inflammation and cutaneous chemical carcinogenesis. Carcinogenesis. 2012; 33:694-701.
- Sahu RP, Yao Y, Konger RL, Travers JB. Platelet-activating Factor does not Mediate UVB-induced Local Immune Suppression. Photochemistry and Photobiology. 2012; 88:490-3.
- DaSilva SC, Sahu RP, Konger RL, Perkins SM, Kaplan MH, Travers JB. Increased skin barrier disruption by sodium lauryl sulfate in mice expressing a constitutively active STAT6 in T cells. Arch Dermatol Res. 2012; 304(1):65-71.
- Lupov IP, Voiles L, Han L, Schwartz A, Dela Rosa M, Oza K, Pelloso D, Sahu RP, Travers JB, Robertson MJ, Chang HC. Acquired STAT4 deficiency as a consequence of cancer chemotherapy. Blood. 2011; 118: 6097-106.
- Sahu RP, Batra S, Brown TL, Srivastava SK. The role of K-Ras gene mutation in TRAIL-induced apoptosis in pancreatic and lung cancer cells. Cancer Chemotherapy and Pharmacology. 2011; 67(2):481-487.
- Boreddy SR, Sahu RP, Srivastava SK. Benzyl Isothiocyanate Suppresses Pancreatic Tumor Angiogenesis and Invasion by inhibiting HIF-1α/VEGF/Rho-GTPases: Pivotal Role of STAT-3. PLOS One. 2011; 6(10):e25799.
- Batra S#, Sahu RP#, Kandala PK, Srivastava SK. Benzyl Isothiocyanate mediated histone deacetylase inhibition leads to turn-off of NF-κB in human pancreatic carcinoma cell lines. (# are equal contributors) Molecular Cancer Therapeutics. 2010; 9(6):1596-608.
- Sahu RP, Epperly MW, Srivastava SK. Benzyl isothiocyanate sensitizes human pancreatic cancer cells to radiation therapy. Frontiers in Bioscience (Elite Ed). 2009;1:568-76.
- Wicker CA, Sahu RP, Kulkarni-Datar K, Srivastava SK, Brown TL. BITC Sensitizes Pancreatic Adenocarcinomas to TRAIL-induced Apoptosis. Cancer Growth Metastasis. 2010; 2009(2): 45-55.
- Sahu RP, Zhang R, Batra S, Shi Y, Srivastava SK. Benzyl isothiocyanate-mediated generation of reactive oxygen species causes cell cycle arrest and induces apoptosis via activation of MAPK in human pancreatic cancer cells. Carcinogenesis. 2009; 30(10):1744-1753.
- Sahu RP, Batra S, Srivastava SK. Activation of ATM/Chk1 by curcumin causes cell cycle arrest and apoptosis in human pancreatic cancer cells. British Journal of Cancer. 2009;100(9): 1425-1433.
- Sahu RP, Srivastava SK. The role of STAT-3 in the induction of apoptosis in pancreatic cancer cells by benzyl isothiocyanate. Journal of National Cancer Institute. 2009;101(3):176-193.
- Shi Y, Sahu RP, Srivastava SK. Triphala inhibits both in vitro and in vivo xenograft growth of pancreatic tumor cells by inducing apoptosis. BMC Cancer. 2008;8:294.
- Zhang R, Humphreys I, Sahu RP, Shi Y, Srivastava SK. In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway. Apoptosis. 2008;13(12):1465-78.
University of Pittsburgh Medical Center, Pittsburgh, PA
Texas Tech University Health Sciences Center, Amarillo, TX
Indiana University School of Medicine, Indianapolis, IN
B.S.: University of Allahabad, Allahabad, India
M.S.: Dr. R.M.L. Avadh University, Faizabad, India
Ph.D.: Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India