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Dr. Rajender K. Motiani

Assistant Professor
E-mail: rajender dot motiani at rcb dot res dot in

  • B.V.Sc. (D.V.M.) 2007, Nagpur Veterinary College, India
  • Ph.D. 2012, Albany Medical College, New York, USA
  • Post Ph.D., Albany Medical College and Regional Centre for Biotechnology
  • INSPIRE Faculty, Institute of Genomics and Integrative Biology, New Delhi

Our laboratory employs multidisciplinary approaches for understanding: 1) Role of Mitochondrial Biology in Cancer Metastasis and 2) Calcium Signaling in Skin Pigmentation. We extensively utilize cell and molecular biology tools, high-end microscopy, electrophysiology, genomics approaches and in vivo animal models for addressing the research problems. The details of ongoing projects in the laboratory are as follows:

Cancer Metastasis

Most of the cancer-associated deaths are due to metastasis of primary tumor. Cancer metastasis is a complex phenomenon that involves tumor angiogenesis (formation of new blood vessels in tumor microenvironment) and loss of endothelial barrier function both at the site of primary tumors (intravasation) and at the secondary sites (extravasation). Although tumor metastasis is widely studied, the critical step of intravasation remains poorly understood. Moreover, the key targetable regulators of intravasation are particularly inadequately defined. Mitochondrial biology plays a critical role in regulating cellular physiology. However, its influence on endothelial function remains under-appreciated. Therefore, our aim is to examine the role of mitochondrial biology in endothelial cell function and identify key mitochondrial proteins regulating tumor cell intravasation. We are utilizing cell and molecular biology tools, live cell and confocal microscopy along with animal models such as zebrafish and mice for addressing this particular research question. The long-term goal of this program is to identify targetable proteins and devise strategies for therapeutically managing them for abrogating tumor cell metastasis.

Skin pigmentation

Skin pigmentation plays a vital role in protection against harmful ultra violet (UV) rays. Indeed, tanning is a protective response of the melanocytes for guarding skin from UV induced cancers. Perturbations in pigmentation pathways result in pigmentary disorders like solar lentigo, melasma, and vitiligo. These disorders are considered as social stigma; impart long-term psychological trauma and are huge economical burden on the health care system. The current therapeutic regimes are not efficient in alleviating pigmentation defects. Therefore, it is critical to identify the novel molecular players regulating pigmentation and devise strategies to target them for calibrating pigmentation. For identifying novel regulators of pigmentation, we performed microarrays on hyperpigmented and hypopigmented primary human melanocytes. Interestingly, we observed significant deviations in the Ca2+ homeostasis in these differentially pigmented cells. However, the significance of Ca2+ dynamics and functional relevance of Ca2+ handling proteins in pigmentation biology remains poorly appreciated. Therefore, we aim to delineate the Calciomics (studies of Ca2+ handling proteins, their interactome and downstream effector proteins) of pigmentation. In a landmark study, we have recently identified an ER Ca2+ sensor protein STIM1 as a novel molecular player that regulates both melanoma growth and pigmentation. Our studies show that STIM1 via its ability to activate two independent second messenger-signaling cascades (Ca2+ and cAMP) induces skin tumor growth and pigmentation. Further using zebrafish and mice models, we validated STIM1’s critical role in stimulating pigmentation and potentiating melanoma formation in vivo. One of the ongoing projects under the ambit of this program is focused on understanding further molecular details of this unique function of STIM1. Going forward, we aim to decipher the role of key Ca2+ handling proteins in pigmentation. This program will employ live cell imaging, electrophysiology, cell and molecular biology tools and genomics approaches for prioritization of the leads and in vivo validation will be performed in zebrafish and mice models. After recognizing the key players modulating pigmentation, we aim to develop strategies for targeting them therapeutically for calibrating skin pigmentation.

  • DST-International Travel Award for attending and serving as Discussion Leader at Gordon Research Conference (Calcium Signaling) Italy, 2017
  • INSPIRE Faculty Award 2013
  • International Travel Award for oral presentation at Gordon Research Seminar (Calcium Signaling) Pisa, Italy 2013
  • Young Investigator Award, Regional Center for Biotechnology 2012
  • Best Graduate Student Alumni Award, Albany Medical College, USA, 2012
  • National Travel Award for oral presentation at Gordon Research Seminar (Calcium Signaling) Maine, USA, 2011
  • Richard H. Edmonds Leadership Award, Albany Medical College, USA, 2010
  • Annual Alumni Research Award, Albany Medical College, USA, 2009
  • Pre-Doctoral Fellowship, Albany Medical College, USA, 2007-2012
  • All India Rank 2294 in All India Pre Medical Test, 2002
  • All India Rank 170 in All India Pre Veterinary Test, 2002
  • We are looking for diligent students and recent PhDs to join the group. Feel free to contact for the possibilities of joining the lab for pursuing Ph.D. and Post Ph.D. training. We would be happy to sponsor deserving candidates for Post Doctoral fellowships.
    • Vashisht A, Tanwar J and Motiani RK#. Regulation of proto-oncogene Orai3 by miR18a/b and miR34a. Cell Calcium 2018 Nov; 75:101-111

    • Motiani RK#, Tanwar J, Raja DA, Vashisht A, Khanna S, Sharma S, Srivastava S, Sivasubbu S, Natarajan VT and Gokhale RS# (2018). STIM1 activation of adenylyl cyclase 6 connects Ca2+ and cAMP signaling during melanogenesis. EMBO Journal. 2018 Mar 1;37(5)

    • Tanwar J and Motiani RK# (2018). Role of SOCE architects STIM and Orai proteins in Cell Death. Cell Calcium 2018 Jan; 69:19-27

    • Nissim TB, Zhang X, Elazar A, Roy S, Stolwijk JA, Zhou Y, Motiani RK, Gueguinou M, Hempel N, Gill DL, Trebak M and Sekler I (2017). Mitochondria control store-operated Ca2+ entry through Na+ and redox signals. EMBO Journal. 2017 Mar 15; 36(6):797-815

    • Tanwar J, Trebak M and Motiani RK# (2017). Role of STIM and Orai proteins in Vascular Disorders. Adv Exp Med Biol. 2017; 993:425-452

    • Kundu S, Bansal S, Muthukumarasamy KM, Sachidanandan C, Motiani RK# and Bajaj A# (2017). Deciphering the role of hydrophobic and hydrophilic bile acids in angiogenesis using in vitro and in vivo model systems. Med Chem Comm. 2017 8 (12), 2248-2257

    • Singh VP*, Motiani RK*, Singh A, Malik G, Aggarwal R, Singh KP, Wani MR, Gokhale SB, Natarajan VT, Gokhale RS (2016). Water Buffalo (Bubalus bubalis) as a spontaneous animal model of Vitiligo. Pigment Cell Melanoma Res. 2016 Jul;29(4):465-9

    • Singh M, Bansal S, Kundu S, Bhargava P, Singh A, Motiani RK, Shyam R, Vedagopuram S, Sengupta S and Bajaj A (2015). Synthesis, Structure-Activity Relationship, and Mechanistic Investigation of Lithocholic Acid Amphiphiles for Colon Cancer Therapy. Med Chem Comm. 2015, Jan: 6(1);192-201

    • Vashisht A, Trebak M and Motiani RK# (2015). STIM and Orai Proteins as novel targets for Cancer therapy. Am J Physiol: Cell Physiol. 2015 Oct 1;309(7):C457-69

    • Singh M, Kundu S, Amarendar Reddy M, Vedagopuram S, Motiani RK, Sengupta S, Srivastava A and Bajaj A (2014). Injectable small molecule hydrogel as a potential nanocarrier for localized and sustained in vivo delivery of doxorubicin. Nanoscale, 2014 Oct 9;6(21):12849-55

    • Motiani RK, Zhang X, Harmon KE, Keller RS, Matrougui K, Bennett JA & Mohamed Trebak (2013). Orai3 is an Estrogen Receptor α-Regulated Ca2+ Channel that Promotes Tumorigenesis. FASEB Journal. 2013 Jan; 27(1): 63-75

    • Motiani RK, Hyzinski-García MC, Zhang X, Henkel M, Mongin AA and Trebak M (2013). STIM1 and Orai1 mediate CRAC channel activity and are essential for human glioblastomas invasion. Pflugers Arch-European Journal of Physiology. 2013 Sep; 465(9):1249-60

    • González-Cobos JC, Zhang X, Zhang W, Ruhle B, Motiani RK, Schindl R, Muik M, Bisaillon JM, Shinde AV, Fahrner M, Singer HA, Matrougui K, Barroso M, Romanin C and Trebak M. (2013). Store-Independent Orai1/3 channels Activated by Intracrine LeukotrineC4 in Neointimal Hyperplasia. Circ. Res. 2013 March 29; 112(7):1013-25

    • Motiani RK, Stolwijk J, Newton RL, Zhang X and Trebak M (2013). Emerging roles of Orai3 in Patho-Physiology. Channels (Austin). Vol. 7(5): 392-401

    • Shinde AV, Motiani RK, Zhang X, Abdullaev IF, Adam AP, Gonzalez-Cobos JC, Matrougui K, Vincent PA and Trebak M. (2013). STIM1 controls endothelial barrier function independently of Orai1 and Ca2+ entry. Science Signaling. 2013 Mar 19;6(267):ra18

    • Merlet E, Atassi F, Motiani RK, Mougenot N, Jacquet A, Nadaud S, Capiod T, Trebak M, Lompré AM and Marchand A (2013). miR-424/322 regulates vascular smooth muscle cell phenotype and neointimal formation in rat. Cardiovascular Research. 2013 Jun 1;98(3):458-68

    • Trebak M, Zhang W, Ruhle B, Henkel MM, González-Cobos JC, Motiani RK, Stolwijk J, Newton RL and Zhang X. (2013). What role for Store Operated Ca2+ Entry in muscle? Microcirculation. 2013 May;20(4):330-6

    • Zhang X, Gonzalez-Cobos JC, Schindl R, Muik M, Ruhle B, Motiani RK, Bisaillon JM, Zhang W, Fahrner M, Borroso M, Matrougui K, Romanin C and Trebak M (2013). Mechanisms of STIM1 Activation of Store-Independent Leukotriene C4-Regulated Ca2+ Channels. Mol Cell Biol. 2013 Sep; 33(18):3715-23

    • Vedagopuram S, Bansal S, Motiani RK, Kundu S, Muppu SK, Majumdar TD, Panjamurthy K, Sengupta S and Bajaj A (2013). Design, synthesis, and mechanistic investigations of Bile Acid-Tamoxifen conjugates for breast cancer therapy. Bioconjug Chem. 2013 Sep 18; 24(9):1468-84

    • Spinelli A*, González-Cobos JC*, Zhang X*, Motiani RK*, Rowan S, Garrett J, Zhang W, Matrougui K, Vincent PA, Singer HA and Trebak M. (2012). STIM1 and Orai1 mediate PDGF-induced airway smooth muscle migration. Pflugers Arch-European Journal of Physiology. November 2012; 464(5): 481-92

    • Motiani RK and Trebak M (2012). STIM1/Orai1-Mediated Store-Operated Calcium Entry in Cardiovascular Disease. Chapter 20 p301-325: Cardiovascular system; Store-operated Ca2+ Entry (SOCE) Pathways: Emerging Signaling Concepts in Human (PATHO) Physiology Springer Publishing Group. ISBN: 978-3-7091-0961-8

    • González-Cobos JC, Zhang X, Motiani RK, Harmon KE and Trebak M (2012). TRPs to Cardiovascular Disease. Chapter 1.1: TRPs and Cardiovascular Diseases; TRP Channels in Drug Discovery: Methods in Pharmacology and Toxicology. Springer/Humana Press. ISBN 978-1-62703-094-6. DOI: 10.1007/978-1-62703-095-3_1.

    • Zhang W, Halligan KE, Zhang X, Bisaillon JM, Gonzalez-Cobos JC, Motiani RK, Hu G, Vincent PA, Zhou J, Barroso M, Singer HA, Matrougui K and Trebak M (2011).Orai1-mediated ICRAC is essential for Neointima formation after Vascular Injury. Circ. Res. 2011 Aug 19;109(5):534-42

    • Potier M*, González JC*, Motiani RK*, Abdullaev IF, Bisaillon JM, Singer HA and Trebak M (2009). Evidence for STIM1- and Orai1-Dependent Store-Operated Ca2+ Influx Through ICRAC in Primary Vascular Smooth Muscle Cells. FASEB Journal. 2009 Aug;23(8):2425-37

    • Zayed N, Afif H, Chabane N, Mfuna-Endam L, Benderdour M, Martel-Pelletier J, Pelletier JP, Motiani RK, Trebak M, Duval N, Fahmi H (2008). Inhibition of interleukin-1beta-induced matrix metalloproteinases 1 and 13 production in human osteoarthritic chondrocytes by prostaglandin D2. Arthritis Rheum. 2008 Nov;58(11):3530-40

    • Abdullaev IF, Bisaillon JM, Potier M, González JC, Motiani RK and Trebak M (2008). Stim1 and Orai1 Mediate CRAC Currents and Store-Operated Calcium Entry important for Endothelial Cell Proliferation. Circ Res. 2008 Nov 21; 103(11):1289-99

    • *Co-first author & #Corresponding author

    Rajender K Motiani
    Regional Centre for Biotechnology
    NCR Biotech Science Cluster
    3rd Milestone, Faridabad-Gurgaon Expressway
    P.O. Box No. 3, Faridabad - 121 001
    Haryana (NCR Delhi), India
    E-mail: rajender dot motiani at rcb dot res dot in
    Phone: 91 129-2848800 

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