Vickram Ramkumar <email@example.com>
Research Interest and Specialties:
The major interest of my laboratory is to determine how cells handle oxidative stress conditions which are produced by conditions such as ischemia and exposure to certain drugs – such as aminoglycoside antibiotics and anticancer drugs. The current research efforts involve studying oxidative stress in the auditory system and in different cancers.
Auditory system: Our initial work examined the adenosine/adenosine receptor system as a modulator of oxidative stress and showed that activation of this system reduces oxidative stress by activating antioxidant enzymes which mediate negative feedback inhibition of the expression of different receptors in this system. Activation of these receptors (mainly the A1 adenosine receptors) plays an important role in the auditory system, where they protect against oxidative stress-induced hearing loss produced by noise and chemotherapeutic drugs. In peripheral nerves, we show that oxidative stress induce the expression of pain receptors, namely transient receptor potential vanilloid 1 (TRPV1) channels which could contribute to inflammatory pain. TRPV1 is also expressed in hair cells in the inner ear (cochlea) which facilitates cisplatin ototoxicity. Blockade of these channels in the inner ear provides protection against cisplatin and noise-induced hearing loss. Activation of TRPV1 by capsaicin in the inner ear promotes a transient inflammatory response mediated by STAT1 and STAT3 transcription factors. We show that this mode of TRPV1 activation preconditions the cochlea to subsequent acoustic trauma and that this preconditioning response is mediated by STAT3. We propose that the ratio of STAT3:STAT1 is a key determinant of cell fate in response to acoustic trauma or ototoxic drugs. Accordingly, agents which increase STAT3 or decrease STAT1 would provide otoprotection.
Prostate cancer: We shown that oxidative stress induce growth and metastasis of prostate cancers through regulation of growth factor and microRNA/miR-21 and long non-coding RNAs (lncRNA) signaling. Drugs which inhibit oxidative stress in these cells, such as adenosine A3 receptor agonists, or inhibit miR-21 (such as resveratrol) decrease the growth and metastasis in prostate cancer.
Education & training
- Ramkumar V, Ravi R, Wilson MC, Gettys TW, Whitworth C, Rybak LP (1994). Identification of A1 adenosine receptors in rat cochlea coupled to inhibition of adenylyl cyclase. Am J Physiol 267(3 Pt 1):C731-C737.
- Ford MS, Nie Z, Whitworth C, Rybak LP, Ramkumar V (1997) Up-regulation of adenosine receptors in the cochlea by cisplatin. Hear Res 111:143-52.
- Ramkumar V, Whitworth CA, Pingle SC, Hughes LF, Rybak LP (2004) Noise induces A1adenosine receptor expression in the chinchilla cochlea. Hear Res 188:47-56.
- Whitworth CA, Ramkumar V, Jones B, Tsukasaki N, Rybak LP (2004) Protection against cisplatin ototoxicity by adenosine agonists. Biochem Pharmacol 67:1801-1807.
- Mukherjea D, Jajoo S, Whitworth CA, Rybak LP, Ramkumar V (2008) Short Interfering (si)RNA Against Transient Receptor Potential Vanilloid-1 (TRPV1) Attenuates Cisplatin-Induced Hearing Loss in the Rat. J Neurosci 28:13056-13065.
- Jajoo S, Mukherjea D, Watabe K and Ramkumar V (2009) Adenosine A3 Receptor Suppresses Prostate Cancer Metastasis by Inhibiting NADPH Oxidase Activity. Neoplasia 11:1132–1145.
- Mukherjea D, Jajoo S, Kaur T, Sheehan KE, Ramkumar V and Rybak LP (2010) Transtympanic Administration of Short Interfering (si)RNA for the NOX3 Isoform of NADPH Oxidase protects against cisplatin-induced hearing loss in the rat. Antioxid Redox Signal 13:589-598.
- Mukherjea D, Jajoo S, Sheehan KE, Kaur T, Sheth S, Bunch J, Perro C, Rybak LP and Ramkumar V (2011) NOX3 NADPH oxidase couples transient receptor potential vanilloid 1 to STAT1-mediated inflammation and hearing Loss. Antioxid Redox Signal 14:999-1010.
- Kaur T, Mukherjea D, Sheehan K, Jajoo S, Rybak L and Ramkumar V (2011) Short interfering RNA against STAT1 attenuates cisplatin induced ototoxicity in the rat by suppressing inflammation. Cell Death Dis 2:e180. doi: 10.1038/cddis.2011.63.
- Sheth S, Jajoo S, Kaur T, Mukherjea D, Sheehan K, Rybak LP, Ramkumar V. Resveratrol reduces prostate cancer growth and metastasis by inhibiting the Akt/MicroRNA-21 pathway. PLoS One. 2012;7(12):e51655.
- Jajoo S, Mukherjea D, Kaur T, Sheehan KE, Sheth S, Borse V, Rybak LP, Ramkumar V. Essential Role of NADPH Oxidase-Dependent Reactive Oxygen Species Generation in Regulating MicroRNA-21 Expression and Function in Prostate Cancer. Antioxid Redox Signal.19:1863-1876.
- Brito R, Sheth S, Mukherjea D, Rybak LP, Ramkumar V (2014) TRPV1: A potential drug target for treating various diseases. Cells 3:517-545. doi: 10.3390/cells3020517.
- Sheth S, Tupal S, Ramkumar V (2015) Role of adenosine receptors in cancer. In Adenosine Signaling Mechanisms: Pharmacology, Functions and Therapeutic Aspects (Ramkumar V and Paes de Carvalho R, editors), Nova Publishers Inc, New York.
- Ramkumar V, Borse V, Ghosh S, Kaur T, Sheehan K, Sheth S, Dhukhwa A, Tupal S, Mukherjea D, Rybak LP (2015) Role of adenosine receptors in auditory functions. In Adenosine Signaling Mechanisms: Pharmacology, Functions and Therapeutic Aspects (Ramkumar V and Paes de Carvalho R, editors), Nova Publishers Inc, New York.
- Kaur T, Borse V, Sheehan K, Sheth S, Ghosh S, Jajoo S, Mukherjea D, Rybak LP, Ramkumar V (2016) Adenosine A1 receptor protects against cisplatin ototoxicity by suppressing the NOX3/STAT1 inflammatory pathway in the cochlea. J Neurosci 36:3962-77.
Grant Title: Transplatin: A novel agent to mitigate cisplatin toxicity (Ramkumar, PI)
Funding Agency: National Cancer Institute (R01CA166907)
Project Period: 07/01/2013 - 06/30/2018
Grant Title: Endogenous modulation of cochlear injury.
Funding Agency: National Institute on Deafness and Other Communicative Disorders (R01DC002396)
Project Period: 03/15/2014 – 03/14/2019