NIBMG

Kaushik Das

Email: kd3@nibmg.ac.in
Present Position: Ramalingaswami Fellow
Highest Educational Qualification: PhD

Profile

Research Interest:

Understanding the role of coagulation proteases in inflammatory diseases.
Deciphering the contribution of coagulation proteases in the treatment of bleeding disorders.
Elucidating the role of coagulation proteases in cancer.

Selected Publications

· Das K, Keshava S, Mukherjee T, Rao LVM.* (2024). Activated protein C-released endothelial extracellular vesicles: A potential mechanism for their cytoprotective effects. Blood. https://doi.org/10.1182/blood.2023023518 [IF : 20.3].
· Das K, Keshava S, Kolesnick R, Pendurthi UR, Rao LVM.* (2024). miR10a enrichment in FVIIa-released endothelial extracellular vesicles: Potential mechanisms. J Thromb Haemost. https://doi.org/10.1016/j.jtha.2023.10.021 [IF : 10.4].
· Das K,* Keshava S, Mukherjee T, Wang J, Magisetty J, Kolesnick R, Pendurthi UR, Rao LVM.* (2023). Factor VIIa releases phosphatidylserine-enriched EVs from endothelial cells by activating acid sphingomyelinase. J Thromb Haemost. https://doi.org/10.1016/j.jtha.2023.08.025 [IF : 10.4].
· Kondreddy V, Keshava S, Das K, Magisetty J, Rao LVM,* Pendurthi UR.* (2022). Gab2-MALT1 Axis Regulates Thromboinflammation and Deep Vein Thrombosis. Blood. https://doi.org/10.1182/blood.2022016424 [IF : 20.3].
· Das K, Pendurthi UR, Manco-Johnson M, Martin EJ, Brophy DF, Rao LVM.* (2022). Factor VIIa Treatment Increases Circulating Extracellular Vesicles in Hemophilia Patients: Implications for the Therapeutic Hemostatic Effect of FVIIa. J Thromb Haemost. https://doi.org/10.1111/jth.15768 [IF : 10.4].
· Magisetty J, Kondreddy VKR, Keshava S, Das K, Esmon CT, Pendurthi UR, Rao LVM.* (2022). Selective inhibition of activated protein C anticoagulant activity protects against hemophilic arthropathy. Blood. https://doi.org/10.1182/blood.2021013119 [IF : 20.3].
· Das K, Keshava S, Pendurthi UR, Rao LVM.* (2022). Factor VIIa suppresses inflammation and barrier disruption through the release of EEVs and transfer of microRNA10a. Blood. https://doi.org/10.1182/blood.2021012358 [IF : 20.3].
· Das K, Keshava S, Ansari SA, Kondreddy V, Esmon CT, Griffin JH, Pendurthi UR, Rao LVM.* (2021). Factor VIIa induces extracellular vesicles from the endothelium: A potential mechanism for its hemostatic effect. Blood. https://doi.org/10.1182/blood.2020008417 [IF : 20.3].
· Das K, Paul S, Singh A, Ghosh A, Roy A, Ansari SA, Prasad R, Mukherjee A, Sen P.* (2019). Triple negative breast cancer-derived microvesicles transfer microRNA221 to the recipient cells and thereby promote epithelial-to-mesenchymal transition. J Biol Chem. https://doi.org/10.1074/jbc.RA119.008619 [IF : 5.5].
* Corresponding Author
PUBMED LINK: My NCBI Collection 64049425 - PubMed (nih.gov)

Research

1. Blood coagulation and inflammation. The activation of blood coagulation yields proteases that interact with specific cell surface receptors to induce inflammatory response. Inflammation, on the other hand, can lead to the activation of blood coagulation.
2. Blood coagulation and cancer. Cancer often triggers the activation of blood coagulation which in turn promotes tumor development and metastasis.
3. Cancer and inflammation.  Many cancers arise from the site of infection, leading to inflammation. Inflammatory cells, on the other hand, release chemicals such as reactive oxygen species (ROS) which induces cancer through mutations in the DNA. The image was created with Biorender.com.

Understanding the role of coagulation proteases in inflammation: Blood coagulation and inflammation are intrinsically related; coagulation-associated inflammatory response is often observed in various pathophysiological conditions. Apart from their common role in coagulation, coagulation proteases often exert intracellular signaling via the activation of protease-activated receptors (PARs). However, the mechanism by which coagulation proteases influences inflammatory response is not completely understood. The primary goal of our lab in this context will be deciphering the mechanism by which different coagulation proteases influence inflammatory responses in various pathophysiological conditions such as sepsis. Understanding the mechanistic insight will aid developing therapeutic targets in controlling different inflammatory diseases. On the other hand, how different inflammatory molecules influence coagulation will also be elucidated in this context.

Deciphering the role coagulation proteases in the treatment of bleeding disorders: Blood coagulation is a tightly controlled biological process which prevents bleeding upon injury to the blood vessels. Defects in the coagulation process often lead to the development of hypo coagulation conditions like hemophilia, thrombocytopenia, von Willebrand disease (VWD) etc. Coagulation factor replacement therapy has been used successfully in the treatment of such diseased conditions. However, the shortcoming of such a therapeutic strategy is the short half-life of the clotting factors which demands multiple and frequent infusions, rendering the treatment highly expensive. The primary objective of this project is to understand the mechanisms by which clotting proteases exert hemostatic effects in such diseased conditions. Targeting the underlying signature molecule/s could be a novel and cost-effective therapeutic means in the treatment of such bleeding episodes in low developed and developing countries.

Investigating the role of coagulation proteases in cancer: Studies have indicated that certain cancers such as colorectal cancer, lung cancer, brain cancer etc. manifest high risk of venous thromboembolism (VTE), leading to increased mortality of such patients. However, the contribution of blood coagulation proteases in the development of such cancers remains ill-defined. The primary thirst of our lab in this broad area is to understand how different coagulation proteases influence cancer development via the modulation of cancer growth, proliferation, metastasis, angiogenesis, apoptosis, stemness, drug resistance, and immune evasion. Understanding the mechanistic details help in the development of potential therapeutics which could be used in combination of conventional therapeutic drugs to target the development of such cancers, thereby improving patients’ survival.

The lab is in need of Ph.D. students. Interested candidates having their own fellowships (such as qualified CSIR/UGC NET, DST Inspire, etc.) can apply.

CV

Education

SI No.	Degree	Year	University
1	Ph.D.	2019	Indian Association for the Cultivation of Science (IACS), Kolkata
2	M.Sc.	2011	Acharya Prafulla Chandra (APC) College, New Barrackpore; Affiliated to West Bengal State University
3	B.Sc.	2009	Surendranath College, Kolkata; Affiliated to the University of Calcutta

Professional Appointments

SI No.	Position	Year	Institute
1	DBT Ramalingaswami Fellow	2024	Biotechnology Research and Innovation Council-National Institute of Biomedical Genomics (BRIC-NIBMG), Kalyani, DBT, India
2	Postdoctoral Research Associate	2019-2024	The University of Texas at Tyler Health Science Center (UTTHSC), Texas, USA

Professional Membership

SI No.	Position	Year	Organization
1	Associate Member	2021	American Society of Hematology (ASH)

Awards/Honors

SI No.	Award/Honor	Year	Organization
1	Judith Graham Pool (JGP) Postdoctoral Fellowship	2020	National Hemophilia Foundation (NHF), USA
2	Institutional Fellowship	2019	Indian Association for the Cultivation of Science (IACS), Department of Science & Technology (DST), India
3	Senior Research Fellowship (SRF)	2016	Council of Scientific & Industrial Research (CSIR), India
4	Graduate Aptitude Test in Engineering (Life Science)	2013	Jointly by Indian Institutes of Technology (IIT) and the National Coordination Board – Graduate Aptitude Test in Engineering (NCB-GATE), Ministry of Human Resource Development (MHRD), India
5	National Eligibility Test (NET)-Junior Research Fellowship (JRF)	Dec-2012	Jointly by Council of Scientific & Industrial Research (CSIR) – University Grant Commission (UGC)
6	Joint Graduate Entrance Examination for Biology and Interdisciplinary Life Sciences (JGEEBILS) / Tata Institute of Fundamental Research (TIFR) Nationwide Entrance Examination GS2013 Biology	2012	Jointly by Tata Institute of Fundamental Research (TIFR) and National Centre for Biological Sciences (NCBS)
7	Indian Institute of Science (IISC) Entrance Test	2012	Indian Institute of Science (IISC)
8	Graduate Aptitude Test in Engineering (Life Science)	2012	Jointly by Indian Institutes of Technology (IIT) and the National Coordination Board – Graduate Aptitude Test in Engineering (NCB-GATE), Ministry of Human Resource Development (MHRD), India
9	Summer Intern	2011	Department of Microbiology, I.P.G.M.E. & R., Kolkata, India

Conference poster/talk

SI No.	Conference	Year	Organizer
1	UGC-Sponsored National Level Seminar (Poster)	2011	Department of Microbiology, Ramakrishna Mission Vidyamandira in collaboration with Bose Institute, Kolkata
2	An Interdisciplinary Approach to Biological Sciences (IABS) (Poster)	2015	Indian Association for the Cultivation of Science, Kolkata
3	Recent Advances in Biotechnology (Poster)	2015	Department of Biotechnology, Visva-Bharati University, Shantiniketan
4	National Science Day (Talk)	2015	Department of Biological Chemistry, Indian Association for the Cultivation of Science, Kolkata
5	An Interdisciplinary Approach to Biological Sciences (IABS) (Poster)	2018	Indian Association for the Cultivation of Science, Kolkata
6	An Interdisciplinary Approach to Biological Sciences (IABS) (Poster)	2023	Indian Association for the Cultivation of Science, Kolkata

Publications

1. Das K, Keshava S, Mukherjee T, Rao LVM.* (2024). Activated protein C-released endothelial extracellular vesicles: A potential mechanism for their cytoprotective effects. Blood. https://doi.org/10.1182/blood.2023023518 [IF : 20.3].

2. Das K, Keshava S, Kolesnick R, Pendurthi UR, Rao LVM.* (2024). miR10a enrichment in FVIIa-released endothelial extracellular vesicles: Potential mechanisms. J Thromb Haemost. https://doi.org/10.1016/j.jtha.2023.10.021 [IF : 10.4].

3. Das K,* Keshava S, Mukherjee T, Wang J, Magisetty J, Kolesnick R, Pendurthi UR, Rao LVM.* (2023). Factor VIIa releases phosphatidylserine-enriched EVs from endothelial cells by activating acid sphingomyelinase. J Thromb Haemost. https://doi.org/10.1016/j.jtha.2023.08.025 [IF : 10.4].

4. Das K,* Paul S, Ghosh A, Gupta S, Mukherjee T, Shankar P, Sharma A, Keshava S, Chauhan SC, Kashyap VK, Parashar D.* (2023). Extracellular Vesicles in Triple–Negative Breast Cancer: Immune Regulation, Biomarkers, and Immunotherapeutic Potential. Cancers. https://doi.org/10.3390/cancers15194879 [IF : 5.2].

5. Paul S, Das K, Ghosh A, Chatterjee A, Bhoumick A, Basu A, Sen P.* (2023). Coagulation factor FVIIa enhances PD-L1 expression and its stability in breast cancer cells to promote breast cancer immune evasion. J Thromb Haemost. https://doi.org/10.1016/j.jtha.2023.08.008 [IF : 10.4].

6. Das K,* Paul S, Mukherjee T, Ghosh A, Sharma A, Shankar P, Gupta S, Keshava S,* Parashar D.* (2023). Beyond Macromolecules: Extracellular Vesicles as Regulators of Inflammatory Diseases. Cells. https://doi.org/10.3390/cells12151963 [IF : 6.0].

7. Das K,* Mukherjee T, Shankar P. (2023). The Role of Extracellular Vesicles in the Pathogenesis of Hematological Malignancies: Interaction with Tumor Microenvironment; a Potential Biomarker and Targeted Therapy. Biomolecules. https://doi.org/10.3390/biom13060897 [IF : 5.5].

8. Das K, Rao LVM.* (2022). The Role of microRNAs in Inflammation. Int J Mol Sci. https://doi.org/10.3390/ijms232415479 [IF : 5.6].

9. Wang J,* Keshava S, Das K, Pendurthi UR, Kolesnick R, Xiang XC, Rao LVM.* (2023). Alterations to sphingomyelin metabolism affect hemostasis and thrombosis. Arterioscler Thromb Vasc Biol. https://doi.org/10.1161/ATVBAHA.122.318443 [IF : 8.7].

10. Singh A, Das K, Banerjee S,* Sen P.* (2023). Elucidation of the signaling pathways for enhanced exosome release from Mycobacterium infected macrophages and subsequent induction of differentiation. Immunology. https://doi.org/10.1111/imm.13561 [IF : 6.4].

11. Kondreddy V, Keshava S, Das K, Magisetty J, Rao LVM,* Pendurthi UR.* (2022). Gab2-MALT1 Axis Regulates Thromboinflammation and Deep Vein Thrombosis. Blood. https://doi.org/10.1182/blood.2022016424 [IF : 20.3].

12. Das K, Pendurthi UR, Manco-Johnson M, Martin EJ, Brophy DF, Rao LVM.* (2022). Factor VIIa Treatment Increases Circulating Extracellular Vesicles in Hemophilia Patients: Implications for the Therapeutic Hemostatic Effect of FVIIa. J Thromb Haemost. https://doi.org/10.1111/jth.15768 [IF : 10.4].

13. Magisetty J, Kondreddy VKR, Keshava S, Das K, Esmon CT, Pendurthi UR, Rao LVM.* (2022). Selective inhibition of activated protein C anticoagulant activity protects against hemophilic arthropathy. Blood. https://doi.org/10.1182/blood.2021013119 [IF : 20.3].

14. Das K, Keshava S, Pendurthi UR, Rao LVM.* (2022). Factor VIIa suppresses inflammation and barrier disruption through the release of EEVs and transfer of microRNA10a. Blood. https://doi.org/10.1182/blood.2021012358 [IF : 20.3].

15. Das K, Keshava S, Ansari SA, Kondreddy V, Esmon CT, Griffin JH, Pendurthi UR, Rao LVM.* (2021). Factor VIIa induces extracellular vesicles from the endothelium: A potential mechanism for its hemostatic effect. Blood. https://doi.org/10.1182/blood.2020008417 [IF : 20.3].

16. Malik S, Prasad R, Das K, Sen P.* (2021). Alcohol functionality in the fatty acid backbone of sphingomyelin guides the inhibition of blood coagulation. RSC Adv. https://doi.org/10.1039/d0ra09218e [IF : 3.9].

17. Bhattacharya A, Ghosh P, Prasad R, Ghosh A, Das K, Roy A, Mallik S, Sinha DK, Sen P.* (2020). MAP Kinase driven actomyosin rearrangement is a crucial regulator of monocyte to macrophage differentiation. Cell Signal. https://doi.org/10.1016/j.cellsig.2020.109691 [IF : 4.8].

18. Mondal L, Mukherjee B,* Das K, Bhattacharya S, Dutta D, Chakraborty S, Paul MM, Gaonkar RH, Debnath MC. (2019). CD-340 functionalized doxorubicin-loaded nanoparticle induces apoptosis and reduces tumor volume along with drug-related cardiotoxicity in mice. Int J Nanomedicine. https://doi.org/10.2147/IJN.S220740 [IF : 8.0].

19. Das K, Paul S, Singh A, Ghosh A, Roy A, Ansari SA, Prasad R, Mukherjee A, Sen P.* (2019). Triple negative breast cancer-derived microvesicles transfer microRNA221 to the recipient cells and thereby promote epithelial-to-mesenchymal transition. J Biol Chem. https://doi.org/10.1074/jbc.RA119.008619 [IF : 5.5].

20. Das K, Prasad R, Singh A, Bhattacharya A, Roy A, Mallik S, Mukherjee A, Sen P.* (2018). Protease-Activated Receptor 2 promotes actomyosin dependent transforming microvesicles generation from human breast cancer. Mol Carcinogen. https://doi.org/10.1002/mc.22891 [IF : 4.6].

21. Das K, Prasad R, Ansari SA, Roy A, Mukherjee A, Sen P.* (2018). Matrix metalloproteinase-2: A key regulator in coagulation proteases mediated human breast cancer progression through autocrine signaling. Biomed Pharmacother. https://doi.org/10.1016/j.biopha.2018.05.155 [IF : 7.5].

22. Das K, Prasad R, Roy S, Mukherjee A, Sen P.* (2018). The Protease Activated Receptor2 Promotes Rab5a Mediated Generation of Pro-metastatic Microvesicles. Sci Rep. https://doi.org/10.1038/s41598-018-25725-w [IF : 4.6].

23. Roy A, Prasad R, Bhattacharya A, Das K, Sen P.* (2017). Role of Tissue Factor-FVIIa Blood Coagulation Initiation Complex in Cancer. Springer Singapore. https://link.springer.com/chapter/10.1007/978-981-10-2513-6_6 (Book Chapter)

24. Roy A, Ansari SA, Das K, Prasad R, Bhattacharya A, Mallik S, Mukherjee A, Sen P.* (2017). Coagulation factor VIIa-mediated protease-activated receptor 2 activation leads to β-catenin accumulation via the AKT/GSK3β pathway and contributes to breast cancer progression. J Biol Chem. https://doi.org/10.1074/jbc.M116.764670 [IF : 5.5].

* Corresponding Author