Hari Koul, Ph.D.

Professor and Carroll Feist Endowed Chair      

                  

Contact Information:

Email: hkoul@lsuhsc.edu
Office Phone: 318-675-8770                        
Laboratory Phone: 318-675-6539
Office Fax: 318-675-5180

Education/Training:

B.Sc. - 1984, (Biology & Chemistry) Kashmir University
M.Sc. - 1986, (Biochemistry) Kashmir University
Ph.D. - 1990, (Biochemistry) Postgraduate Institute of Medical Education and Research

Major Research Interests:

Our current research program is based on following original observations:

We pioneered the field of oxalate nephrotoxicity and made the first direct demonstration of toxic effects of oxalate in the renal epithelial cells, and over the years we defined the signaling mechanisms and inflammatory cascades associated with oxalate and calcium oxalate crystals.
We identified tumor metastasis function of Sam Pointed Domain Ets Factor (SPDEF) and demonstrated that SPDEF expression is decreased with increasing Gleason grade in prostate cancer.
We discovered that oxidant stress is inherent in prostate cancer cells and is required for maintenance of an aggressive phenotype.
We discovered that hypoxia/re-oxygenation differentially affects cancer cells and normal cells. We observed that upon hypoxia/re-oxygenation, normal epithelial cells undergo cell death, while cancer cells display an aggressive phenotype.
We are specifically interested in two interrelated drivers of tumor progression: 1) Role of Red-Ox signaling and accompanying pathways in tumor progression and metastasis; and 2) Role of transcriptional reprogramming as driver of tumor progression and metastasis. Along these areas, we have four ongoing studies: Project one is aimed at evaluating the role of NOX4 activation in tumor progression via transcriptional reprograming in cancer cells with special emphasis on epigenetic regulation; Project two is aimed at evaluating the role of Unfolded Protein Response in tumor progression and metastasis and leveraging unresolved UPR as therapeutic strategy in cancer; Project three is aimed at understanding the regulatory mechanism and functional consequences of alterations in expression of putative metastasis suppressor SPDEF in prostate cancer; and, Project four is aimed at deciphering transcriptional reprograming in prostate cancer progression and metastasis with special emphasis on Androgen Receptor signaling and transcription factor abundance. Data from these four projects feeds our fifth project aimed at development of small molecules for targeted therapy of solid tumors. Another area of my research is to understand the mechanism/s that drive oxalate and calcium oxalate crystal induced chronic inflammatory process/es and dysfunction of renal epithelial cells, with a long-term objective to identify actionable targets to prevent oxalate nephropathy, kidney stone disease and end stage renal disease.

Representative Publications:

  1. Tetrandrine (TET) Induces Death Receptors: Apo Trail R1 (DR4) and Apo Trail R2 (DR5) and sensitizes Prostate Cancer Cells to TRAIL induced apoptosis.
  2. Androgen receptor (AR) cistrome in prostate differentiation and cancer progression.
  3. The transcription factor SPDEF suppresses prostate tumor metastasis.
  4. Partial bladder outlet obstruction in mice may cause E-cadherin repression through hypoxia induced pathway.
  5. Oxalate upregulates expression of IL-2Rβ and activates IL-2R signaling in HK-2 cells, a line of human renal epithelial cells.

All Publications: Pubmed