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Suhasini Joshi, PhD

Research Fellow

Lab Phone

+1 (646) 888-2216

 

The primary area of my research interest is the field of cancer biology, which sparked since I joined Department of Biochemistry at All India Institute of Medical Sciences (AIIMS, India) for Master of Sciences (M.Sc.) program in 2007. During the program, I have been instrumental in the identification of novel diagnostic and therapeutic targets for Multiple Myeloma (MM), a B-cell malignancy, and successfully established Angiopoietins as novel diagnostic markers in MM, primarily using clinical samples. Though here I was obtaining enough exposure in clinical sciences, I became more inclined to understand the mechanism by which normal cells transform to malignant cells. Fortunately, I received an opportunity in October 2009 to perform research at NorthShore University Health System, affiliated under Northwestern University. Here, my research projects were centered on field carcinogenesis and chemoprevention strategies against colorectal cancer.  Subsequently, I joined the Department of Biochemistry and Molecular Biology at University of Nebraska Medical Center to pursue my doctorate degree. My previous work in the field of cancer biology especially on the translational aspect, prompted me to join Dr. Batra, whose lab primarily focuses on elucidating pathobiological implications of mucins in cancer condition. The principal objective of my doctorate thesis was to elucidate the novel regulatory mechanisms and functions of MUC4 mucin, a high molecular-weight glycoprotein that is one of the top-differentially expressed proteins in pancreatic cancer (PC). Briefly, I have studied the implications of tumor microenvironment on aberrant MUC4 expression at both cellular and acellular levels. In short, for the first time, I elucidated the importance of MUC4 degradation by starving and hypoxic PC cells for their survival. I also showed the role of bile acids, which are known to create proinflammatory environment in colorectal cancer, in the progression of pancreatic cancer. Functionally, I demonstrated the novel role of MUC4 oncoprotein in the stabilization of EGFR receptor, which is known to be indispensable for PC development.

As discussed, my graduate research work primarily focused on micro-environmental stress in PC, I devise a rationale that stress plays an important role in PC pathobiology from initiation to its full development. After gaining further insight in this field by attending various research conferences, meeting, seminars and readings, I comprehended that tumor transformation has a selective advantage in terms of proliferation, anti-apoptosis and against other physiological stress. In this context, molecular chaperones emerged as potential targets due to their oncogenic activity. With the goal of furthering my experiences in Pharmacology and Translational Research, I am currently working as a Postdoctoral Fellow under the supervision of Dr. Gabriela Chiosis since August 2016. During my studies, I came to understand that the PC microenvironment is highly dynamic and in constant change leading to the birth of new adaptive responses in order to maintain the overall cellular equilibrium and tissue homeostasis. Upregulation of chaperone proteins and their rewiring into stable networks with tumor surviving functions, which we have coined as the epichaperome, is one of the major adaptive responses acquired by cancer to prevent stress-induced apoptosis. Thus, strategies aimed to manipulate cellular stress in PC could yield therapeutic benefit due to the established importance of stress in the malignant transformation and progression of PC. During my postdoctoral fellowship training, I will utilize mechanistic and therapeutic strategies discovered in Dr. Chiosis’ lab to manipulate and target these predominant stress-based mechanisms.

Publications


  1. Joshi, S.; Cruz, E; Rachagani, S; Guha, S; Brand, R. E.; Ponnusamy, M. P.; et al.; Bile acids-mediated overexpression of MUC4 via FAK-dependent c-Jun activation promotes the aggressiveness of pancreatic cancer. Mol Oncol. 2016, 10 (7), 1063-1077

  2. Joshi, S.; Kumar, S.; Ponnusamy, M. P.; Batra, S. K.; Hypoxia-induced oxidative stress promotes MUC4 degradation via autophagy to enhance pancreatic cancer cells survival. Oncogene 2016, 35 (45), 5882-5892

  3. Joshi, S.; Gupta, N.;  Khan, R.;  Kumar, R.;  Sharma, M.;  Kumar, L, Sharma, A.; Interrelationship between angiogenesis, inflammation and oxidative stress in Indian patients with multiple myeloma. Clin. Transl. Oncol. 2016, 18 (2), 132-137.

  4. Kumar, S; Cruz, E.; Joshi, S.; Patel, A.; Jahan, R.; Batra, S. K.; Jain, M.; Genetic Variants of Mucins: Unexplored Conundrum. Carcinogenesis 2016. [Epub ahead of print]

  5. Kumar, S.; Das, S.; Rachagani, S.;  Kaur, S.;  Joshi, S.;  Johansson, S.L.; Ponnusamy, M.P.; Jain, M.; Batra, S. K.; NCOA3-mediated upregulation of mucin expression via transcriptional and post-translational changes during the development of pancreatic cancer. Oncogene 2015, 34 (37), 4879-4889.

  6. Lakshmanan, I.; Seshacharyulu, P.; Haridas, D.; Rachagani, S.; Gupta, S.; Joshi, S.; Guda, C.; Yan, Y.; Jain, M.;, Ganti, A. K.; Ponnusamy, M. P.; Batra, S. K.; Novel HER3/MUC4 oncogenic signaling aggravates the tumorigenic phenotypes of pancreatic cancer cells. Oncotarget  2015, 6 (25), 21085-21099.

  7. Joshi, S.; Kumar, S.; Bafna, S.; Rachagani, S.; Jain, M.; Wagner, K. U.; Batra S. K.; Genetically-Engineered Mucins Mouse Models for Inflammation and Cancer. Cancer Metastasis Rev. 2015, 34 (4), 593-609.  

  8. Kumar, S.; Torres, M. P.; Kaur, S.; Rachagani, S.; Joshi, S.; Johansson, S. L.; Momi, N.; Baine, M. J.; Gilling, C. E.; Smith, L. M.; Wyatt, T. A.; Jain, M.; Joshi, S. S.; Batra, S. K.; Smoking accelerates pancreatic cancer progression by promoting differentiation of MDSCs and inducing HB-EGF expression in macrophages. Oncogene 2015, 34 (16), 2052-2060.

  9. Joshi, S.; Kumar, S.; Choudhary, A.; Ponnusamy, M. P.; Batra, S. K.; Altered Mucins (MUC) Trafficking in Benign and Malignant Conditions. Oncotarget 2014, 5 (17), 7272-7284.

  10. Torres, M. P.; Rachagani S.; Purohit V.; Pandey P.; Joshi S.; Moore E, D.; Johansson, S. L.; Singh, P. K.; Ganti, A. K.; Batra, S. K.; Graviola: A Novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism. Cancer. Lett. 2012, 323 (1), 29-40.

  11. Qi, W.; Joshi, S.; Weber, C. R.; Wali, R. K.; Roy, H. K.; Savkovic, S. D.; Polyethylene glycol diminishes pathological effects of Citrobacter rodentium infection by blocking bacterial attachment to the colonic epithelia. Gut Microbes 2011, 2 (5), 267-273.

  12. Joshi, S.; Khan, R.; Sharma, M.; Kumar, L.; Sharma, A.; Angiopoietin-2: A potential novel diagnostic marker in multiple myeloma. Clin. Biochem. 2011, 44 (8-9), 590-595.

  13. Roy, H.K.; Koetsier, J. L.; Tiwari, A. K.; Joshi, S.; Kunte, D. P.; Ward, T. P.; Gandhi, S. R.; Wali, R. K.; Involvement of p21cip1/waf1 in the anti-proliferative effects of polyethylene glycol in colon carcinogenesis. Int. J Oncol. 2011, 38 (2), 529-536.

  14. Qi, W.; Weber, CR.; Wasland, K.; Roy, H.; Wali, R.; Joshi, S.; Savkovic, S. D.; Tumor suppressor FOXO3 mediates signals from the EGF receptor to regulate proliferation of colonic cells. Am. J. Physiol. Gastrointest. Liver. Physiol. 2011, 300 (2), G264-272.

  15. Joshi, S.; K Tiwari, A.; Mondal, B.; Sharma, A.; Oncoproteomics. Clin Chim Acta. 2010. 412 (3-4); 217-226.

  16. Sharma, A.; Khan, R.; Joshi, S.; Sharma, M.; Kumar, L.; Dysregulation in Th1/Th2 cytokines ratios in Multiple myeloma patients. Leuk. Lymphoma 2010, 51 (5), 920-927.