Sougat Misra

Sougat Misra

  • Assistant Research Professor
  • Member, Next-Generation Therapies, Penn State Cancer Institute
202 AVBS Building
Shortlidge Road

University Park, PA 16802

Areas of Expertise

  • Experimental Drug Development with specific focus on Acute Myeloid Leukemia
  • Development of ex vivo organotypic tissue slice cultures of human solid tumors as experimental model systems
  • Biochemical Toxicology
  • Redox Biology
  • Selenium in human Health and Diseases

Education

  • Ph.D. - Department of Biology, University of Saskatchewan, Canada

Biography

I am trained as a biochemical toxicologist from the Department of Biology, University of Saskatchewan, Canada from where I earned my Ph.D. in September 2011. My graduate studies involved deciphering the mechanistic underpinnings of cytotoxic effects of several naturally-occurring small molecule selenium compounds using primary isolated hepatocytes as a model system. I subsequently moved to the Department of Laboratory Medicine, Karolinska Institute, Sweden initially as a Post-Doctoral fellow and was later recruited as an Assistant Professor in 2015 until 2019. My research at Karolinska Institute delved into targeting redox anomaly of malignant cells as a therapeutic modality. To this end, I have invented a novel therapeutic strategy to target cancer cells with high specificity employing selected small molecule redox active compounds. In addition, I have pioneered a state-of-the-art method for ex vivo organotypic tissue slice culture of human pancreatic ductal adenocarcinoma. This 3-dimensional tissue slice culture model offers a unique possibility in precision cancer medicine for efficacy testing of cancer therapeutics in patient’s own malignant tissue outside of their body prior to adjuvant chemotherapy.

Research Interests

Equilibrium of redox-regulatory processes play pivotal role in human health. Systemic redox imbalances have been associated with many human diseases and conditions, including cancer and inflammation. Comprising both basic sciences and translational studies, I investigate “how dynamic equilibrium of cellular and systemic redox-regulatory processes can be pharmacologically manipulated for therapeutic gain"?

My current research activities at Penn State University delve into two independent areas.

  1. The primary focus of my translational research is to evaluate the efficacy of diverse range of redox-reactive small molecules as experimental cancer therapeutics using relevant in vitro, ex vivo and in vivo murine models of cancer. Inspired by the current trends in cancer drug discovery, novel combinatorial treatment strategies are devised to strengthen the anti-cancer efficacy of selected small molecules to elicit cancer cell death. Range of approaches to target malignant cells include, but not limited to, synthetic RNA- and small molecules-guided manipulation of the key pharmacological properties of the cell death-inducing small molecules.
  2. The physiological functions of several selenoproteins remains largely unknown. I employ transcriptomics, metabolomics, cellular energy metabolism, and other pertinent tools in cell biology and biochemistry to study how the genetic loss of selected selenoproteins alters the biological functions of immune cells, mainly macrophages.

In summary, the overreaching goal of my research is pharmacological manipulations of systemic redox imbalances in a specific manner, such that oxidative stress-associated diseases or conditions can be mitigated, managed, or cured based on the contextual causal or consequential relationship between the stressors and the pathophysiological disorders.

Funding Support

  • Harbaugh Harbaugh Undergraduate Research Assistantship (HURA)
  • Research Applications for Innovation (RAIN) Grant
  • American Cancer Society (Institutional Research Grant)
  • NSF I-Crops Grant
  • Horace T. Woodward Faculty Development Fund
  • MIST Funding, an intramural start-up funding from PSU

Publications

Articles in peer-reviewed Journals

   Cancer biology and therapeutics

  1. Brodin, O. ; Hackler, J. ; Misra, S. ; Wendt, S.; Sun, Q.; Laff, E.; Stoppe, C.; Bjornstedt, M.; Schomburg, L., Selenoprotein P as Biomarker of Selenium Status in Clinical Trials with Therapeutic Dosages of Selenite. Nutrients, 2020. 12(4), 1067. Shared first author.
  2. Misra, S.; Selvam, A. K.; Wallenberg, M.; Ambati, A.; Matolcsy, A.; Magalhaes, I.; Lauter, G.; Bjornstedt, M., Selenite promotes all-trans retinoic acid-induced maturation of acute promyelocytic leukemia cells. Oncotarget 2016, 7 (46), 74686-74700. Joint Corresponding Author.
  3. Flouda, K.; Dersch, J. M.; Gabel-Jensen, C.; Stürup, S.; Misra, S.; Björnstedt, M.; Gammelgaard, B., Quantification of low molecular weight selenium metabolites in human plasma after treatment with selenite in pharmacological doses by LC-ICP-MS. Analytical and Bioanalytical Chemistry 2016, 1-9. Results from a Phase I clinical trial.
  4. Brodin, O.; Eksborg, S.; Wallenberg, M.; Asker-Hagelberg, C.; Larsen, E. H.; Mohlkert, D.; Lenneby-Helleday, C.; Jacobsson, H.; Linder, S.; Misra, S.; Björnstedt, M., Pharmacokinetics and toxicity of sodium selenite in the treatment of patients with carcinoma in a phase I clinical trial: The SECAR study. Nutrients 2015, 7 (6), 4978-4994. Results from a Phase I clinical trial.
  5. Wallenberg, M.; Misra, S.; Wasik, A. M.; Marzano, C.; Björnstedt, M.; Gandin, V.; Fernandes, A. P., Selenium induces a multi-targeted cell death process in addition to ROS formation. J Cell Mol Med 2014, 18 (4), 671-684.
  6. Fernandes, A. P.; Wallenberg, M.; Gandin, V.; Misra, S.; Tisato, F.; Marzano, C.; Rigobello, M. P.; Kumar, S.; Björnstedt, M., Methylselenol Formed by Spontaneous Methylation of Selenide Is a Superior Selenium Substrate to the Thioredoxin and Glutaredoxin Systems. PLoS ONE 2012, 7 (11).

   Cancer model development

  1. Misra, S., Moro, C.F.; Chiaro, M. D.; Puoso, S.; Sebestyén, A.; Löhr, M.; Bjornstedt, M.; Verbeke, C.S., Ex vivo organotypic culture system of precision-cut slices of human pancreatic ductal adenocarcinoma. Scientific Reports, 2019. Article Number: 2133, One of the top 30 articles published in Scientific Reports in 2019.

   Transcription factor

  1. Sugiaman-Trapman, D.; Vitezic, M.; Jouhilahti, E. M.; Mathelier, A.; Lauter, G.; Misra, S.; Daub, C. O.; Kere, J.; Swoboda, P., Characterization of the human RFX transcription factor family by regulatory and target gene analysis. BMC Genomics 2018, 19 (1), 181.

   Biochemical Toxicology

  1. Misra, S.; Peak, D.; Chen, N.; Hamilton, C.; Niyogi, S., Tissue-specific accumulation and speciation of selenium in rainbow trout (Oncorhynchus mykiss) exposed to elevated dietary selenomethionine. Comparative Biochemistry and Physiology - C Toxicology and Pharmacology 2012, 155 (4), 560-565.
  2. Misra, S.; Kwong, R. W. M.; Niyogi, S., Transport of selenium across the plasma membrane of primary hepatocytes and enterocytes of rainbow trout. Journal of Experimental Biology 2012, 215 (9), 1491-1501.
  3. Misra, S.; Hamilton, C.; Niyogi, S., Induction of oxidative stress by selenomethionine in isolated hepatocytes of rainbow trout (Oncorhynchus mykiss). Toxicology in Vitro 2012, 26 (4), 621-629.
  4. Misra, S.; Peak, D.; Niyogi, S., Application of XANES spectroscopy in understanding the metabolism of selenium in isolated rainbow trout hepatocytes: Insights into selenium toxicity. Metallomics 2010, 2 (10), 710-717.
  5. Misra, S.; Niyogi, S., Selenite causes cytotoxicity in rainbow trout (Oncorhynchus mykiss) hepatocytes by inducing oxidative stress. Toxicology in Vitro 2009, 23 (7), 1249-1258.

   Nutrition and Biochemistry

  1. Xavier, B.; Sahu, N. P.; Pal, A. K.; Jain, K. K.; Misra, S.; Dalvi, R. S.; Baruah, K., Water soaking and exogenous enzyme treatment of plant-based diets: Effect on growth performance, whole-body composition, and digestive enzyme activities of rohu, Labeo rohita (Hamilton), fingerlings. Fish Physiology and Biochemistry 2012, 38 (2), 341-353.
  2. Yengkokpam, S.; Pal, A. K.; Sahu, N. P.; Jain, K. K.; Dalvi, R.; Misra, S.; Debnath, D., Metabolic modulation in Labeo rohita fingerlings during starvation: Hsp70 expression and oxygen consumption. Aquaculture 2008, 285 (1-4), 234-237.
  3. Biswas, P.; Pal, A. K.; Sahu, N. P.; Reddy, A. K.; Prusty, A. K.; Misra, S., Lysine and/or phytase supplementation in the diet of Penaeus monodon (Fabricius) juveniles: Effect on growth, body composition and lipid profile. Aquaculture 2007, 265 (1-4), 253-260.
  4. Misra, S.; Sahu, N. P.; Pal, A. K.; Xavier, B.; Kumar, S.; Mukherjee, S. C., Pre- and post-challenge immuno-haematological changes in Labeo rohita juveniles fed gelatinised or non-gelatinised carbohydrate with n-3 PUFA. Fish and Shellfish Immunology 2006, 21 (4), 346-356.

Invited Review Articles

  1. Fenghua, Q, Misra, S., and Prabhu, Sandeep. K. (2020). Selenium and selenoproteins in prostanoid metabolism and immunity. Critical Reviews in Biochemistry and Molecular Biology 54, 484-516.
  2. Misra, S., Boylan, M., Selvam, A., Spallholz, J. E. and Björnstedt, M. (2015). Redox-active selenium compounds—from toxicity and cell death to cancer treatment. Nutrients 7, 3536-3556.
  3. Wallenberg, M., Misra, S. and Björnstedt, M. (2014). Selenium cytotoxicity in cancer. Basic and Clinical Pharmacology and Toxicology 114, 377-386. Joint First Author.

Invited Book Chapters

  1. Misra, S., and Bjornstedt, M. (2018). Selenocystine and cancer. In Selenium (Michalke, Bernhard Eds.), Molecular and Integrative Toxicology Series, Springer Publication, Amsterdam. Corresponding Author.
  2. Selvam, A.K., Bjornstedt, M., and Misra, S. (2018). Therapeutic potential of selenium compounds in the treatment of cancer. In Selenium (Michalke, Bernhard Eds.), Molecular and Integrative Toxicology Series, Springer Publication, Amsterdam. Corresponding Author.
  3. Misra, S. and Bjornstedt, M. (2017). Metabolism of selenium/selenocystine and their roles in the prevention and treatment of human cancer. In Organoseenium compounds in Biology and Medicine, Royal Society of Chemistry, London, UK. Corresponding Author.
  4. Misra, S., Wallenberg, M., Brodin, O., Bjornstedt, M. (2015). Selenite in Cancer Therapy. In Diversity of Selenium Functions in Health and Disease (R. Brigelius-Flohe, Sies, Helmut, Eds.), pp. 400. CRC Press, Boca Raton.

 Invited Lectures

  1. Misra, S. “Discovery of a novel therapeutic strategy that selectively targets cancer cells”. Institute of Life Sciences, Bhubaneswar, India. November 2017.
  2. Misra, S. “Development of an organotypic slice culture of pancreatic tumors as an ex vivo model system to study tumor biology and drug testing”. 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. February 2017.
  3. Misra, S. “Therapeutic potential of selenium compounds in cancer”. Tata Memorial Cancer Centre, ACTREC, Mumbai, India. November 2017.
  4. Misra, S. “Organic selenium compounds: review of current knowledge and research on their combined blend of antioxidant, pro-oxidant and antitumor effects”. Department of Pharmacology, Karolinska Institute, Sweden. May 2017.