Haribabu Bodduluri, Ph.D.

Education:  

B.S., Chemistry and Biology, Andhra University, India; 1976
M.S., Biochemistry, Andhra University, India; 1978
Ph.D., Biochemistry, Indian Institute of Science, India; 1983
Postdoctoral Fellowship, Department of Biology, The Johns Hopkins University, Baltimore, MD; 1984-1987
Senior Research Associate, Department of Biological Sciences, Hunter College, City University of New York, New York, NY; 1987-1992 

Curriculum Vitae 

Current Positions: 

Professor, Department of Microbiology & Immunology, University of Louisville Health Sciences Center, Louisville, KY
Vice Chair, Professor, Department of Microbiology & Immunology, University of Louisville Health Sciences Center
Member and Co-Leader – Immuno-Oncology Program, James Graham Brown Cancer Center, University of Louisville 

Contact Information: 

Department of Microbiology and Immunology
Clinical & Translational Research Building, 324
505 South Hancock Street
University of Louisville
Louisville, kY 40202
Phone: 502/852-7503
Email: 

Research Description: 

Research in the Bodduluri laboratory is focused on identifying how chemokines control leukocyte migration and tumor development with particular emphasis on leukotriene B4 and its receptors BLT1 and BLT2.  Over the last decade, we developed mouse models and generated novel reagents to examine the function and regulation of BLT1 and BLT2.  These models facilitated the identification of BLT1 as a critical mediator of inflammatory diseases including asthma, atherosclerosis, arthritis and other autoimmune diseases, as well as sleep apnea promoted atherogenesis, and insulin resistance during diet induced obesity.

Our studies on cancer use mouse models of spontaneous cancers of lung and colon that were crossed onto mice deficient in BLT.  These experiments revealed quite unexpected and exciting opportunities for novel clinical intervention of these cancers.  BLT1 is an important mediator of host response to infection and immune surveillance of intestinal cancers.  Our studies showed that exposure to crystalline silica, a common agent encountered in mining and other industries, strongly promotes lung cancer and the absence of BLT1 protects mice from developing silicosis and reduces the lung cancer burden.  Crystalline silica induces the synthesis of LTB4 from mast cells and macrophages that orchestrates neutrophil recruitment through a novel self-perpetuating cascade that results in chronic tumor promoting lung inflammation.  We are currently working out mechanisms involved in this inflammatory cascade so as to develop intervention strategies to prevent silicosis and associated lung cancers.

Our recent observations in models of colon cancer suggest that absence of BLT1 reshapes the gut microbiome to promote colon cancer development.  Absence of BLT1 also was found to significantly impair cytotoxic T-cell mediated anti-tumor immunity in intestinal tumors as well as in implantable melanoma.  In this case, mast mediated LTB4 acts to recruit CD8+ T-cells and our current studies are aimed at understanding the mechanistic implications of these findings to determine how LTB4/BLT1 axis could mediate both tumor promoting and tumor suppressive mechanisms depending on the anatomical location of the tumors.  Using structure-based virtual screening strategies many novel compounds that are agonists and/or antagonists to BLT1 were identified.  Further studies on preclinical development of these compounds are ongoing in our laboratory. 

Literature Cited: 

  1.  Jala VR, Shao WH, Haribabu B.  Phosphorylation-independent beta-arrestin translocation and internalization of leukotriene B4 receptors.  Journal of Biological Chemistry 2005 Feb 11;280(6):4880-7.  doi: 10.1074/jbc.M409821200.  Epub 2004 Nov 23.  PMID: 15561704.
  2. Allendorf DJ, Yan J, Ross GD, Hansen RD, Baran JT, Subbarao K, Wang L, Haribabu B.  C5a-mediated leukotriene B4-amplified neutrophil chemotaxis is essential in tumor immunotherapy facilitated by anti-tumor monoclonal antibody and beta-glucan.  Journal of Immunology 2005 Jun 1;174(11):7050-6.  doi: 10.4049/jimmunol.174.11.7050.  PMID: 15905548.
  3. Basu S, Jala VR, Mathis S, Rajagopal ST, Del Prete A, Maturu P, Trent JO, Haribabu B.  Critical role for polar residues in coupling leukotriene B4 binding to signal transduction in BLT1.  Journal of Biological Chemistry 2007 Mar 30;282(13):10005-10017.  doi: 10.1074/jbc.M609552200.  Epub 2007 Jan 21.  PMID: 17237498.
  4. Estrada R, Zeng Q, Lu H, Sarojini H, Lee JF, Mathis SP, Sanchez T, Wang E, Kontos CD, Lin CY, Hla T, Haribabu B, Lee MJ.  Up-regulating sphingosine 1-phosphate receptor-2 signaling impairs chemotactic, wound-healing, and morphogenetic responses in senescent endothelial cells.  Journal of Biological Chemistry 2008 Oct 31;283(44):30363-75.  doi: 10.1074/jbc.M804392200.  Epub 2008 Sep 2.  PMID: 18765664.  PMCID: PMC25 73088.
  5. Spite M, Hellmann J, Tang Y, Mathis SP, Kosuri M, Bhatnagar A, Jala VR, Haribabu B.  Deficiency of the leukotriene B4 receptor, BLT-1, protects against systemic insulin resistance in diet-induced obesity.  Journal of Immunology 2011 Aug 15;187(4):1942-9.  doi: 10.4049/jimmunol.1100196.  Epub 2011 Jul 8.  PMID: 21742977.  PMCID: PMC3150353.
  6. Sharma RK, Chheda Z, Jala VR, Haribabu B.  Expression of leukotriene B₄ receptor-1 on CD8⁺ T cells is required for their migration into tumors to elicit effective antitumor immunity.  Journal of Immunology 2013 Sep 15;191(6):3462-70.  doi: 10.4049/jimmunol.1300967.  Epub 2013 Aug 19.  PMID: 23960231.  PMCID: PMC3815560.
  7. Hester CM, Jala VR, Langille MG, Umar S, Greiner KA, Haribabu B.  Fecal microbes, short chain fatty acids, and colorectal cancer across racial/ethnic groups.  World Journal of Gastroenterology 2015 Mar 7;21(9):2759-69.  doi: 10.3748/wjg.v21.i9.2759.  PMID: 25759547.  PMCID: PMC4351229.
  8. Deng Z, Mu J, Tseng M, Wattenberg B, Zhuang X, Egilmez NK, Wang Q, Zhang L,Norris J, Guo H, Yan J, Haribabu B, Miller D, Zhang HG.  Enterobacteria-secreted particles induce production of exosome-like S1P-containing particles by intestinal epithelium to drive Th17-mediated tumorigenesis.  Nature Communications 2015 Apr 24;6:6956.  doi: 10.1038/ncomms7956.  Erratum in: Nature Communications 2016;7:11348.  PMID: 25907800.  PMCID: PMC4410277.
  9. Satpathy SR, Jala VR, Bodduluri SR, Krishnan E, Hegde B, Hoyle GW, Fraig M, Luster AD, Haribabu B.  Crystalline silica-induced leukotriene B4-dependent inflammation promotes lung tumour growth.  Nature Communications 2015 Apr 29;6:7064.  doi: 10.1038/ncomms8064.  PMID: 25923988.  PMCID: PMC4418220.
  10. Chheda ZS, Sharma RK, Jala VR, Luster AD, Haribabu B.  Chemoattractant receptors BLT1 and CXCR3 regulate antitumor immunity by facilitating CD8+ T cell migration into tumors.  Journal of Immunology 2016 Sep 1;197(5):2016-26.  doi: 10.4049/jimmunol.1502376.  Epub 2016 Jul 27.  PMID: 27465528.  PMCID: PMC4992661.
  11. Jala VR, Maturu P, Bodduluri SR, Krishnan E, Mathis S, Subbarao K, Wang M, Jenson AB, Proctor ML, Rouchka EC, Knight R, Haribabu B.  Leukotriene B4-receptor-1 mediated host response shapes gut microbiota and controls colon tumor progression.  Oncoimmunology 2017 Aug 10;6(12):e1361593.  doi: 10.1080/2162402X.2017.1361593.  PMID: 29209564.  PMCID: PMC5706601.
  12. Bodduluri SR, Mathis S, Maturu P, Krishnan E, Satpathy SR, Chilton PM, Mitchell TC, Lira S, Locati M, Mantovani A, Jala VR, Haribabu B.  Mast cell-dependent CD8+ T-cell recruitment mediates immune surveillance of intestinal tumors in ApcMin/+ mice.  Cancer Immunology Research 2018 Mar;6(3):332-347.  doi: 10.1158/2326-6066.CIR-17-0424.  Epub 2018 Jan 30.  PMID: 29382671.
  13. Hegde B, Bodduluri SR, Satpathy SR, Alghsham RS, Jala VR, Uriarte SM, Chung DH, Lawrenz MB, Haribabu B.  Inflammasome-independent leukotriene B4 production drives crystalline silica-induced sterile inflammation.  Journal of Immunology 2018 May 15;200(10):3556-3567.  doi: 10.4049/jimmunol.1701504.  Epub 2018 Apr 2.  PMID: 29610142.  PMCID: PMC5940517.
  14. Teng Y, Ren Y, Sayed M, Hu X, Lei C, Kumar A, Hutchins E, Mu J, Deng Z, Luo C, Sundaram K, Sriwastva MK, Zhang L, Hsieh M, Reiman R, Haribabu B, Yan J, Jala VR, Miller DM, Van Keuren-Jensen K, Merchant ML, McClain CJ, Park JW, Egilmez NK, Zhang HG.  Plant-derived exosomal microRNAs shape the gut microbiota.  Cell Host & Microbe 2018 Nov 14;24(5):637-652.e8.  doi: 10.1016/j.chom.2018.10.001.  Epub 2018 Oct 25.  PMID: 30449315.  PMCID: PMC6746408.
  15. Singh R, Chandrashekharappa S, Bodduluri SR, Baby BV, Hegde B, Kotla NG, Hiwale AA, Saiyed T, Patel P, Vijay-Kumar M, Langille MGI, Douglas GM, Cheng X, Rouchka EC, Waigel SJ, Dryden GW, Alatassi H, Zhang HG, Haribabu B, Vemula PK, Jala VR. Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway. Nature Communications 2019 Jan 9;10(1):89.  doi: 10.1038/s41467-018-07859-7.  PMID: 30626868.  PMCID: PMC6327034
  16. Jala VR, Bodduluri SR, Ghosh S, Chheda Z, Singh R, Smith ME, Chilton PM, Fleming CJ, Mathis SP, Sharma RK, Knight R, Yan J, Haribabu B.  Absence of CCR2 reduces spontaneous intestinal tumorigenesis in the ApcMin/+ mouse model.  International Journal of Cancer 2021 Jan 26. doi: 10.1002/ijc.33477. Epub ahead of print. PMID: 33497467.
  17. Ghosh S, Whitley CS, Haribabu B, Jala VR.  Regulation of intestinal barrier function by microbial metabolites.  Cellular & Molecular Gastroenterology & Hepatology 2021;11(5):1463-1482.  doi: 10.1016/j.jcmgh.2021.02.007.  Epub 2021 Feb 18.  PMID: 33610769.  PMCID: PMC8025057.