In this section
Gajendra K Katara, PhD
Gajendra Katara graduated with a PhD in Biosciences from the Birla Institute of Technology, Pilani, India in 2012. During his PhD, he worked on infectious disease immunology and investigated the host immune responses in human visceral leishmaniasis which is caused by an intracellular parasite Leishmania. His research work demonstrated how leishmania parasite simultaneously exploits Th1 and Th2 responses for their survival and growth in the human system. For his postdoctoral research, he joined the laboratory of Professor Kenneth Beaman in Department of Microbiology and Immunology at Rosalind Franklin University of Medicine and Science in 2012 where he started research work on cancer immunology. He studied the involvement of Vacuolar (V)-ATPase in modulating immune responses in the tumor microenvironment in breast cancer. In 2018, he was appointed as Research Assistant Professor of Microbiology and Immunology at RFUMS.
We are interested in the identification of molecules that can serve as biomarkers for
early detection of metastasis and therapy of cancers. Currently, we are investigating the
microenvironmental signals involved in the cancer malignancy and working to define
methods to target these signals. By focusing on cancer malignancy, our ultimate goal is
to help prevent cancer metastasis.
- Tumor Microenvironment. We have worked extensively on the role of V-
ATPase in modulating various components of tumor microenvironment in breast
cancer. In our previous work, we have shown that a2 isoform of V-ATPase (a2V)
is selectively expressed on the surface of cancer cells and the N-terminal peptide
of a2V (a2NTD) stimulates immuno-suppressive phenotype (M2) in
macrophages. Inhibition of a2V expression in cancer cells decreased the number
of M2 macrophages in tumor microenvironment that resulted in decreased breast
tumor growth in mice. Using a conditional a2V knockout mouse model, we have
recently shown that the deletion of a2V in the mammary epithelial cells reduced
the stiffness of extra cellular matrix (ECM) through defective glycosylation of
proteins in Golgi. This reduction in stiffness of ECM contributed to soft tumor
phenotype and increased metastasis of breast tumors. We identified a2V
expression in epithelial cells as a key requirement for proper ECM formation in
breast tissue and its expression levels can significantly modulate breast tumor
dissemination. Evaluation of a2V expression in normal breast tissues can help in
identifying patients with high risk of developing metastases.
- Epithelial-Mesenchymal Transition. EMT is one of the mechanism of invasion
used by the cancer cells for their malignant transformation. We are working to
identify the cellular and subcellular mechanisms behind EMT in breast cancer.
Our recent data demonstrate that IL-22 signaling is crucial for malignant
transformation of cancer cells and interference in IL-22 activity can inhibit EMT
and reduce metastasis in breast cancer. We are now focusing on the
identification of mechanisms behind these observations.
Publications from primary research area
- *Katara GK, Kulshrestha A, Schneiderman S, Ibrahim SA,Riehl VE, Bilal MA, Beaman KD. IL-22 is required for malignancy in breast cancer: Potential target to control cancer metastasis. 2019. (Manuscript submitted)
- Kulshrestha A, Katara GK, Ibrahim SA, et al., Targeting V-ATPase Isoform Restores Cisplatin Activity in Resistant Ovarian Cancer: Inhibition of Autophagy, Endosome Function, and ERK/MEK Pathway,” J Oncol. 2019, Article ID 2343876.
- Sahoo M, Katara GK, Bilal MY, Ibrahim SA, Kulshrestha A, Fleetwood S, Suzue K, Beaman KD. Mammary Epithelium-specific Hematopoietic stem cell specific V-ATPase controls breast cancer progression and metastasis via cytotoxic T cells. Oncotarget. 2018 Sep 4;9(69):33215-33231.
- Katara GK, Kulshrestha A, Mao L, Sahoo M, Wang X, Ibrahim SA, Pamarthy S, Suzue K, Shekhawat GS, Gilman-Sachs A, Beaman KD. Mammary Epithelium-specific Inactivation of V-ATPase Reduces Stiffness of Extracellular Matrix and Enhances Metastasis of Breast Cancer. Mol Oncol 2018; 12: 208-223.
- Pamarthy S, Kulshrestha A, Katara GK, Beaman KD. The curious case of signaling and V-ATPase. Mol Cancer 2018; 17: 41.
- Kulshrestha A*, Katara GK*, Ibrahim SA, Patil R, Patil SA, Beaman KD. Microtubule inhibitor, SP-6-27 inhibits angiogenesis and induces apoptosis in ovarian cancer cells. Oncotarget 2017; 8(40):67017-67028.
* Equal first author contribution
- Patil R, Kulshrestha A, Tikoo A, Fleetwood S, Katara GK, Kolli B, Seibel W, Gilman-Sachs A, Patil SP, Beaman KD. Identification of Novel Bisbenzimidazole derivatives as Anticancer Vacuolar (H+)-ATPase inhibitors. Molecules 2017; 22: 1559.
- modules-15c741539860ed, Kulshrestha A, Jaiswal MK, Pamarthy S, Gilman-Sachs A, Beaman KD. Inhibition of vacuolar ATPase subunit in tumor cells delays tumor growth by decreasing the essential macrophage population in the tumor microenvironment. Oncogene 2016; 35: 1058-1065.
- Kulshrestha A, Katara GK, Ginter J, Pamarthy S, Ibrahim S, Jaiswal MK, Sandulescu C, Periakaruppan R, Dolan J, Gilman-Sachs A, Beaman KD. Selective inhibition of tumor cell associated Vacuolar-ATPase 'a2' isoform overcomes cisplatin resistance in ovarian cancer cells. Mol Oncol 2016; 10:789-805.
- Pamarthy S, Mao S, Katara GK, Fleetwood S, Kulshreshta A, Gilman-Sachs A, Beaman KD. The V-ATPase a2 isoform controls mammary gland development through Notch and TGF-β signaling. Cell Death Dis 2016; 7(11):e2443.
- Ibrahim SA, Kulshrestha A, Katara GK, Amin MA, Beaman KD. Tumor associated vacuolar ATPase promotes neutrophil migration by autocrine secretion of IL-8. Sci Rep 2016; 6:36865.
- Kulshrestha A, Katara GK, Ibrahim S, Pamarthy S, Jaiswal MK, Gilman-Sachs A, Beaman KD. Vacuolar ATPase 'a2' isoform exhibits distinct cell surface accumulation and modulates matrix metalloproteinase activity in ovarian cancer. Oncotarget 2015; 6: 3797-810.
- Ibrahim SA, Katara GK, Kulshrestha A, Jaiswal MK, Magdy AA, Beaman KD. Breast cancer associated a2 isoform vacuolar ATPase immunomodulates neutrophils: potential role in tumor progression. Oncotarget 2015; 6:33033-45.
- Pamarthy S, Jaiswal MK, Kulshreshtha A, Katara GK, Gilman-Sachs A, Beaman KD. The Vacuolar ATPase a2-subunit regulates Notch signaling in triple-negative breast cancer cells. Oncotarget 2015; 6:34206-20.
- Katara GK, Jaiswal MK, Kulshrestha A, Kolli B, Gilman-Sachs A, Beaman KD. Tumor associated vacuolar ATPase subunit promotes tumorigenic characteristics in macrophages. Oncogene 2014; 33: 5649–54.
- Katara GK, Raj A, Kumar R, Avishek K, Kaushal H, Ansari NA, Bumb RA, Salotra P. Analysis of localized immune responses reveals presence of Th17 and Treg cells in cutaneous leishmaniasis due to Leishmania tropica. BMC Immunol 2013; 14: 52.
- Katara GK, Ansari NA, Ramesh V, Salotra P. Evidence for role of Th17 type responses in post kala azar dermal leishmaniasis (PKDL). PLoS Neg Trop Dis 2012; 6: e1703.
- Katara GK, Ansari NA, Verma S, Ramesh V, Salotra P. Foxp3 and IL -10 expression correlates with parasite burden in lesional tissues of post kala azar dermal leishmaniasis (PKDL) patients. PLoS Neg Trop Dis 2011; 5(5): e1171
Publications from other research areas:
- Dembaeva S, Schneiderman S, Jaiswal MK, Agrawal V, Katara GK, Hirsch E, Beaman KD,. IL-22 Prevents Lipopolysaccharide-Induced Preterm Labor in Mice. Biol Reprod. 2018; 98: 299-308.
- Beaman KD, Dambaeva S, Katara GK, Kulshrestha A, Gilman-Sachs A. The immune response in pregnancy and in cancer is active and supportive of placental and tumor cell growth not their destruction. Gynecol Oncol 2017. doi: 10.1016/j.ygyno.2017.04.019.
- Beaman KD, Jaiswal MK, Katara GK, Kulshreshta A, Pamarthy S, Ibrahim S, Kwak-Kim J, Gilman-Sachs A. Pregnancy is a model for tumors, not transplantation. Am J Reprod Immunol 2016; 76: 3-7.
- Jaiswal MK, Agrawal V, Katara GK, Pamarthy S, Kulshrestha A, Chaouat G, Gilman-Sachs A, Beaman KD. Male fertility and apoptosis in normal spermatogenesis are regulated by vacuolar-ATPase isoform a2. J Reprod Immunol. 2015; 112:38-45.
- Agrawal V, Jaiswal MK, Mallers T, Katara GK, Gilman-Sachs A, Beaman KD, Hirsch E. Altered autophagic flux enhances inflammatory responses during inflammation-induced preterm labor. Sci Rep 2015; 5: 9410.
- Jaiswal MK, Agrawal V, Pamarthy S, Katara GK, Kulshrestha A, Gilman-Sachs A, Beaman KD Hirsch E. Notch signaling in inflammation-induced preterm labor. Sci Rep 2015; 5:15221.
- Agrawal V, Jaiswal MK, Pamarthy S, Katara GK, Kulshrestha A, Gilman-Sachs A, Hirsch E, Beaman KD. Role of Notch signaling during lipopolysaccharide-induced preterm labor. J Leukoc Biol. 2015; 100: 261-74.
- Jaiswal MK, Katara GK, Mallers T, Chaouat G, Gilman-Sachs A, Beaman KD. Vacuolar-ATPase isoform a2 regulates macrophages and cytokine profile necessary for normal spermatogenesis in testis. J Leukoc Biol 2014; 96: 337-47.