Rajini Rao

Rajini Rao is an American physiologist who is a professor at Johns Hopkins University School of Medicine. Rao is also the director of the Graduate Program in Cellular and Molecular Medicine and is the principal investigator of the Rao Lab. She is an elected fellow of the American Association for the Advancement of Science, Rao discovers novel ion channels and explores their roles in human health and disease. The Rao Lab identified the oncogenic role of SPCA2 in breast cancer through an aberrant method of signalling to calcium channels.

Early life and education Rao was born in India. She pursued her undergraduate degree in chemistry and biology in 1980 at Mount Carmel College in Bangalore. Rao graduated with a Bachelor of Science in 1983. Rao then moved to the United States to conduct her graduate studies at the University of Rochester in Rochester, New York. In her graduate work, Rao discovered that three catalytic sites in the ATPase enzyme needed to interact to achieve maximal enzymatic rate and that this occurs in a cyclical mechanism. She later found that the binding of ATP to the alpha subunit of the F1-ATPase and the associated conformational changes are abolished when the Lysine-175 residue is mutated. Her work suggests a critical role for this specific residue on the nucleotide binding of ATP to the ATPase enzyme. She used site directed mutagenesis to probe the role of specific amino acid residues in the function of the enzyme. Rao also developed a novel system with which to probe the function and structure of the H+ATPase. Since ATPases are essential for the survival of a cell, mutating them will lead to cell death and render the preparation difficult to study. In 2008, Rao was promoted to director of the Graduate Training Program in Cellular and Molecular Medicine. The lab uses yeast as a model organism with which to study the biology of cation transport channels. A specific isoform of SPCA that is upregulated in breast cancer cells seemed to mediate aberrant calcium signalling, leading to increased calcium influx and promote tumorigenesis. Normally, the transporter mediates increased uptake of glutamate and stabilizes expression of the transferrin receptor and the GLAST transporter. NHE9 is an exchanger of Na+ and H+, and when blocked in glioblastoma it attenuates tumor growth and improves the efficacy of typical glioblastoma treatment, EGFR inhibitors. The Rao Lab found in 2018 that defects in the NHE6 exchanger of Na+ and H+ led to defective clearance of amyloid beta by astrocytes.

Awards and honors 2009: Hans Prochaska Memorial Lecturer at Johns Hopkins 2009: Teacher of the Year Award, The Johns Hopkins University School of Medicine 2009: Johns Hopkins Professors Award for Excellence in Teaching in Preclinical Sciences 2006: Keynote speaker for Pan American Plant Membrane Biology Workshop 2001–2003: Nico Van Uden Keynote Speaker for SMYTE conferences at Crete and Bonn 1994–1997: American Cancer Society Junior Faculty Award

Selected publications Kondapalli, KC, Llongueras, JP, Capilla-Gonzalez, V, Hack, A, Smith, C, Guerrero-Cazares, H, Quinones-Hinojosa, A, and Rao, R. (2015) A leak pathway for luminal protons in endosomes drives oncogenic signaling in glioblastoma. Nature Communications 6 Article number: 6289 doi:10.1038/ncomms7289 Hack A, Schushan M, Landau M, Ben-Tal N, Rao R. "Functional evaluation of autism-associated mutations in NHE9." Nat Commun. 2013;4:2510. doi: 10.1038/ncomms3510. Patenaude C, Zhang Y, Cormack B, Köhler J, Rao R. "Essential role for vacuolar acidification in Candida albicans virulence." J Biol Chem. 2013 Sep 6;288(36):26256-64. doi: 10.1074/jbc.M113.494815. Epub 2013 Jul 24. Cross BM, Hack A, Reinhardt TA, Rao R. "SPCA2 regulates Orai1 trafficking and store independent Ca2+ entry in a model of lactation." PLoS One. 2013 Jun 28;8(6):e67348. doi: 10.1371/journal.pone.0067348. Print 2013. Shim JS, Rao R, Beebe K, Neckers L, Han I, Nahta R, Liu JO. "Selective inhibition of HER2-positive breast cancer cells by the HIV protease inhibitor nelfinavir." J Natl Cancer Inst. 2012 Oct 17;104(20):1576-90. doi: 10.1093/jnci/djs396. Epub 2012 Oct 5. Kondapalli KC, Kallay LM, Muszelik M, Rao R. "Unconventional chemiosmotic coupling of NHA2, a mammalian Na+/H+ antiporter, to a plasma membrane H+ gradient." J Biol Chem. 2012 Oct 19;287(43):36239-50. doi: 10.1074/jbc.M112.403550. Epub 2012 Sep 4. Feng, M., Grice, D., Faddy, H.M., Ngyuen, N., Leitch, S., Wang, Y., Muend, S., Kenny, P.A., Sukumar, S., Roberts-Thomson, S., Monteith, G., and Rao, R. (2010) Store-independent activation of Orai1 by SPCA2 in mammary tumors. Cell 143, 84–98.