Rajini Rao

Last updated
Rajini Rao
Rajini Rao.png
Born
India
NationalityAmerican
Alma mater Mount Carmel College
University of Rochester
Known forPhysiology of cation transport in health and disease
Awards2009 Hans Prochaska Memorial Lecturer, 2009 Johns Hopkins Professors Award for Excellence in Teaching in Preclinical Sciences
Scientific career
FieldsPhysiology, cation transport
Institutions Johns Hopkins School of Medicine

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, [1] 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.

Contents

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. [2] Rao then moved to the United States to conduct her graduate studies at the University of Rochester in Rochester, New York. [2] Under the mentorship of Alan E. Senior, Rao explored the biochemistry of the alpha subunit of Escherichia coli F1-ATPase enzyme. [3] 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. [4] 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. [5] Her work suggests a critical role for this specific residue on the nucleotide binding of ATP to the ATPase enzyme. [5]

Following the completion of her PhD in 1988, Rao pursued postdoctoral work at Yale University in New Haven, Connecticut. [2] Rao worked under the mentorship of Carolyn Slayman to gain experience in the field of genetics. [6] Rao was funded by an American Heart Association Postdoctoral Fellowship from 1990 to 1991. [2]  Rao's work explored the functions of the H+-ATPase in yeast. [7] She used site directed mutagenesis to probe the role of specific amino acid residues in the function of the enzyme. [8] Rao also developed a novel system with which to probe the function and structure of the H+ATPase. [9] Since ATPases are essential for the survival of a cell, mutating them will lead to cell death and render the preparation difficult to study. [9] In order to maintain wildtype expression of ATPases while studying the effects of certain mutations on ATPase function, Rao created a way to rapidly express the mutant ATPase in a secretory vesicle pool such that these vesicles could be isolated to study the catalytics of the enzyme. [9] Following her postdoctoral work, Rao worked for one year as an Associate Research Scientist in the Department of Genetics at Yale University.[ citation needed ]

Career and research

In 1993, Rao was recruited to Johns Hopkins School of Medicine where she became an assistant professor in the Department of Physiology. [2] In 1998, Rao was promoted to associate professor and then in 2004, she became the first female full professor in the Department of Physiology. [10] In 2008, Rao was promoted to director of the Graduate Training Program in Cellular and Molecular Medicine. [10] Rao also acts as a faculty mentor within several other departments at Johns Hopkins and teaches several classes on Pathways and Regulation, the Human Body, and Molecules and Cells. [10] Rao is a member of the American Association of Science the Federation of American Society of Experimental Biology. [2]

As the principal investigator of the Rao Lab, Rao leads a research program focused on exploring the role of intracellular cation transport in health and disease. [6] The lab uses yeast as a model organism with which to study the biology of cation transport channels. [6] The specific transporters they focus on are H+-ATPases, Ca2+-ATPases, and Na+/H+ exchangers. [2] The Rao Lab defined the secretory pathway Ca2+, Mn2+-ATPases (SPCA) and later discovered their roles in breast cancer development. [11] 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. [11]

Cation transporters in neurological disease

After becoming the first to clone the endosomal Na+(K+)/H+ exchanger (eNHE) and recognize it as a separate exchanger from the plasma membrane NHE, the Rao Lab has begun to explore this exchanger in the context of neurological diseases including autism. Alzheimer's Disease, and glioblastoma. [2] Since rare mutations in the NHE gene had been associated with autism, Rao probed the function of autism-associated variants of this transporter. [12] Normally, the transporter mediates increased uptake of glutamate and stabilizes expression of the transferrin receptor and the GLAST transporter. [12] However, the variants of the NHE in autism led to loss of function in the glial cells called astrocytes. [12]  Their finding highlighted the possibility of autism-associated mutations exerting their effects through loss of astrocyte function in the brain. [12]   The Rao Lab then discovered that NHE9 expression in glioblastoma is associated with poor clinical prognosis. [13] 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. [13] Cation channels have also been associated with the pathogenesis of Alzheimer's disease.  [14] 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. [14] Through epigenetic modulation, they were able to restore the ability of NHE6 to maintain alkalinity in the endosome and this improved amyloid beta clearance by astrocytes. [14] In 2020, the Rao group published a review on the role of tumor acidification and cancer metastasis. [15]

Awards and honors

Selected publications

Related Research Articles

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<span class="mw-page-title-main">Glioblastoma</span> Aggressive type of brain cancer

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<i>PTEN</i> (gene) Tumor suppressor gene

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<span class="mw-page-title-main">ATP7A</span> Protein-coding gene in humans

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<span class="mw-page-title-main">Phosphoinositide 3-kinase</span> Class of enzymes

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<span class="mw-page-title-main">Bafilomycin</span> Chemical compound

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<span class="mw-page-title-main">V-ATPase</span> Family of transport protein complexes

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Plasma membrane Ca<sup>2+</sup> ATPase Transport protein

The plasma membrane Ca2+ ATPase (PMCA) is a transport protein in the plasma membrane of cells that functions as a calcium pump to remove calcium (Ca2+) from the cell. PMCA function is vital for regulating the amount of Ca2+ within all eukaryotic cells. There is a very large transmembrane electrochemical gradient of Ca2+ driving the entry of the ion into cells, yet it is very important that they maintain low concentrations of Ca2+ for proper cell signalling. Thus, it is necessary for cells to employ ion pumps to remove the Ca2+. The PMCA and the sodium calcium exchanger (NCX) are together the main regulators of intracellular Ca2+ concentrations. Since it transports Ca2+ into the extracellular space, the PMCA is also an important regulator of the calcium concentration in the extracellular space.

<span class="mw-page-title-main">ORAI1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Methylated-DNA-protein-cysteine methyltransferase</span> Mammalian protein found in Homo sapiens

Methylated-DNA--protein-cysteine methyltransferase(MGMT), also known as O6-alkylguanine DNA alkyltransferaseAGT, is a protein that in humans is encoded by the MGMT gene. MGMT is crucial for genome stability. It repairs the naturally occurring mutagenic DNA lesion O6-methylguanine back to guanine and prevents mismatch and errors during DNA replication and transcription. Accordingly, loss of MGMT increases the carcinogenic risk in mice after exposure to alkylating agents. The two bacterial isozymes are Ada and Ogt.

<span class="mw-page-title-main">Valosin-containing protein</span> Protein-coding gene in the species Homo sapiens

Valosin-containing protein (VCP) or transitional endoplasmic reticulum ATPase also known as p97 in mammals and CDC48 in S. cerevisiae, is an enzyme that in humans is encoded by the VCP gene. The TER ATPase is an ATPase enzyme present in all eukaryotes and archaebacteria. Its main function is to segregate protein molecules from large cellular structures such as protein assemblies, organelle membranes and chromatin, and thus facilitate the degradation of released polypeptides by the multi-subunit protease proteasome.

<span class="mw-page-title-main">ATP2C1</span> Protein-coding gene in the species Homo sapiens

Calcium-transporting ATPase type 2C member 1 is an enzyme that in humans is encoded by the ATP2C1 gene.

<span class="mw-page-title-main">ATP2B2</span> Protein-coding gene in the species Homo sapiens

Plasma membrane calcium-transporting ATPase 2 is an enzyme that in humans is encoded by the ATP2B2 gene.

<span class="mw-page-title-main">ATP5E</span> Protein-coding gene in the species Homo sapiens

ATP synthase F1 subunit epsilon, mitochondrial is an enzyme that in humans is encoded by the ATP5F1E gene. The protein encoded by ATP5F1E is a subunit of ATP synthase, also known as Complex V. Variations of this gene have been associated with mitochondrial complex V deficiency, nuclear 3 (MC5DN3) and Papillary Thyroid Cancer.

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The P-type plasma membrane H+
-ATPase
is found in plants and fungi. For the gastric H+
/K+
ATPase, see Hydrogen potassium ATPase.

Anjana Rao is a cellular and molecular biologist of Indian ethnicity, working in the US. She uses immune cells as well as other types of cells to understand intracellular signaling and gene expression. Her research focuses on how signaling pathways control gene expression.

<span class="mw-page-title-main">Soma Sengupta</span> Scientist and neuro-oncologist

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References

  1. "Ten Johns Hopkins researchers named American Association for the Advancement of Science Fellows" . Retrieved 2023-01-31.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 "Rajini Rao, Ph.D., Professor of Physiology". Johns Hopkins Medicine. Retrieved 2020-05-21.
  3. "Rajini Rao - Google Scholar Citations". scholar.google.com. Retrieved 2020-05-21.
  4. R, Rao; Ae, Senior (1987-12-25). "The Properties of Hybrid F1-ATPase Enzymes Suggest That a Cyclical Catalytic Mechanism Involving Three Catalytic Sites Occurs". The Journal of Biological Chemistry. 262 (36): 17450–4. doi: 10.1016/S0021-9258(18)45400-2 . PMID   2891693.
  5. 1 2 R, Rao; J, Pagan; Ae, Senior (1988-11-05). "Directed Mutagenesis of the Strongly Conserved Lysine 175 in the Proposed Nucleotide-Binding Domain of Alpha-Subunit From Escherichia Coli F1-ATPase". The Journal of Biological Chemistry. 263 (31): 15957–63. doi: 10.1016/S0021-9258(18)37542-2 . PMID   2903146.
  6. 1 2 3 "Rao Lab Homepage". www.bs.jhmi.edu. Retrieved 2020-05-21.
  7. "Rajini Rao - Publications". neurotree.org. Retrieved 2020-05-21.
  8. R, Rao; Cw, Slayman (1993-03-25). "Mutagenesis of Conserved Residues in the Phosphorylation Domain of the Yeast Plasma Membrane H(+)-ATPase. Effects on Structure and Function". The Journal of Biological Chemistry. 268 (9): 6708–13. doi: 10.1016/S0021-9258(18)53307-X . PMID   8454643.
  9. 1 2 3 Rao, R; Slayman, C W (April 1992). "Mutagenesis of the yeast plasma membrane H(+)-ATPase. A novel expression system". Biophysical Journal. 62 (1): 228–237. Bibcode:1992BpJ....62..228R. doi:10.1016/S0006-3495(92)81808-8. ISSN   0006-3495. PMC   1260523 . PMID   1534699.
  10. 1 2 3 "Rajini Rao, PhD". cmm.jhmi.edu. Retrieved 2020-05-21.
  11. 1 2 Feng, Mingye; Grice, Desma M.; Faddy, Helen M.; Nguyen, Nguyen; Leitch, Sharon; Wang, Yingyu; Muend, Sabina; Kenny, Paraic A.; Sukumar, Saraswati; Roberts-Thomson, Sarah J.; Monteith, Gregory R. (2010-10-01). "Store-Independent Activation of Orai1 by SPCA2 in Mammary Tumors". Cell. 143 (1): 84–98. doi:10.1016/j.cell.2010.08.040. ISSN   0092-8674. PMC   2950964 . PMID   20887894.
  12. 1 2 3 4 Kondapalli, Kalyan C.; Hack, Anniesha; Schushan, Maya; Landau, Meytal; Ben-Tal, Nir; Rao, Rajini (2013-09-25). "Functional evaluation of autism-associated mutations in NHE9". Nature Communications. 4 (1): 2510. Bibcode:2013NatCo...4.2510K. doi:10.1038/ncomms3510. ISSN   2041-1723. PMC   3815575 . PMID   24065030.
  13. 1 2 Kondapalli, Kalyan C.; Llongueras, Jose P.; Capilla-González, Vivian; Prasad, Hari; Hack, Anniesha; Smith, Christopher; Guerrero-Cázares, Hugo; Quiñones-Hinojosa, Alfredo; Rao, Rajini (2015-02-09). "A leak pathway for luminal protons in endosomes drives oncogenic signalling in glioblastoma". Nature Communications. 6 (1): 6289. Bibcode:2015NatCo...6.6289K. doi: 10.1038/ncomms7289 . ISSN   2041-1723. PMC   4354686 . PMID   25662504.
  14. 1 2 3 Prasad, Hari; Rao, Rajini (2018-07-10). "Amyloid clearance defect in ApoE4 astrocytes is reversed by epigenetic correction of endosomal pH". Proceedings of the National Academy of Sciences. 115 (28): E6640–E6649. Bibcode:2018PNAS..115E6640P. doi: 10.1073/pnas.1801612115 . ISSN   0027-8424. PMC   6048470 . PMID   29946028.
  15. Ko, Myungjun; Quiñones-Hinojosa, Alfredo; Rao, Rajini (2020-04-06). "Emerging links between endosomal pH and cancer". Cancer and Metastasis Reviews. 39 (2): 519–534. doi:10.1007/s10555-020-09870-1. ISSN   1573-7233. PMC   7316587 . PMID   32253638.