Dr. Ajay Kumar

Principal Scientist

Pharmacology Division

CSIR – Indian Institute of Integrative Medicine, Canal Road, Jammu – 180001
Email: ajaykumar[at]iiim[dot]res[dot]in

Profile

Bio Sketch

Ajay Kumar is a Biologist. His current research interests include autophagy and NLRP3 inflammasome with a particular focus on Alzheimer’s disease and aging. Complex pathophysiology of Alzheimer’s disease (AD) is accompanied by accumulation of amyloid beta (Aβ) and formation of neurofibrillary tangles (NFTs) of TAU in the brain. Deposits of intracellular and extracellular protein aggregates critically affect the normal physiological functions of neurons including neurotransmission and intracellular transport, which finally leads to death of neurons. Autophagy is one of the mechanisms that help in the clearance of these protein deposits from the brain. However, age related slow down and defects in autophagy strongly hampers this clearance.

We have shown in the cellular and transgenic mouse models that pharmacological induction of autophagy can be utilized to clear these proteins from the brain. Our data suggest that clearance of Aβ further ameliorates the AD pathology in 5XFAD mice, which include reduced neuroinflammation and improved learning and memory. We are also trying to understand if age-related decline in brain functioning can be reversed to boost the clearance of these protein by using small molecules. Accumulation of polypeptides also leads to activation of NLRP3 inflammasome and release of IL-1β, which triggers development of inflammatory microenvironment in the brain thus inflicting more damage to neurons. Our data shows a strong relationship between decline of autophagy and NLRP3 mediated inflammation. Therefore, our research interests also include simultaneous targeting of autophagy and NLRP3 inflammasome for development of Alzheimer’s therapeutics.

Education

Degree	Subjects	University	Qualifying Year
Ph.D.	Biotechnology	Panjab University, Chandigarh	2009
M.Sc.	Biotechnology	Panjab University, Chandigarh	2004

Position Held

Position Held	Period	Organization
Principal Scientist	07.07.2022 to Present	CSIR-Indian Institute of Integrative Medicine, Jammu
Senior Technical Officer III	2017 to 06.07.2022	CSIR-Indian Institute of Integrative Medicine, Jammu
Scientist Fellow	2016 to 2017	CSIR-Indian Institute of Integrative Medicine, Jammu

Area of Expertise

Molecular pharmacology, molecular mechanism
regulation and targeting of autophagy in Alzheimer’s disease
NLRP3 inflammasome and neuroinflammation
development of therapeutics against Alzheimer’s disease, brain aging

Project Involved / Ongoing Projects

Projects

Poly-pharmacology approach for development of effective anti-Alzheimer therapeutics – MLP-6002, WP-4
CSIR-Sickle Cell Anemia Mission Project (HCP-0008)
Glucosinolate based immunomodulatory nutraceutical formulation from seeds of Brassica

Publications and Patents

Publications

Authors	Title	Journal
Abubakar Wani, Sweilem B. Al Rihani, Ankita Sharma, Brenna Weadick, Rajgopal Govindarajan, Sameer U. Khan, Parduman R. Sharma, Ashish Dogra, Utpal Nandi, Chilakala N Reddy, Sonali S Bharate, Gurdarshan Singh, Sandip B. Bharate, Ram A. Vishwakarma, Amal Kaddoumi, and Ajay Kumar.	Crocetin promotes clearance of amyloid-β by inducing autophagy via the STK11/LKB1-mediated AMPK pathway.	Autophagy. 2020 (Just accepted)
Abubakar Wani, Mehak Gupta, Masroor Ahmad, Aabid M Shah, Aitizaz Ul Ahsan, Parvaiz H Qazi, Fayaz Malik, Gurdarshan Singh, Parduman R Sharma, Amal Kaddoumi, Sandip B Bharate, Ram A Vishwakarma, and Ajay Kumar	Alborixin clears amyloid-β by inducing autophagy through PTEN mediated inhibition of AKT pathway.	Autophagy. 2019; 15(10):1810-1828., doi 10.1080/15548627.2019.1596476
Mehak Gupta, Abubakar Wani, Aitizaz Ul Ahsan, Mani Chopra, Ram A Vishwakarma, Gurdarshan Singh, and Ajay Kumar	Soluble Aβ1-42 suppresses TNF-α and activates NLRP3 inflammasome in THP-1 macrophages.	Cytokine. 2018; 111:84-87., DOI:10.1016/j.cyto.2018.07.026
Mohd Abdullaha, Shabber Mohammed, Mehboob Ali, Ajay Kumar, Ram A. Vishwakarma, Sandip B. Bharate,	Discovery of Quinazolin-4(3H)-ones as NLRP3 Inflammasome Inhibitors: Computational Design, Metal-Free Synthesis, and in Vitro Biological Evaluation.	Journal of Organic Chemistry. 2019, 849, 5129-5140
Sudhakar Manda, Sadhana Sharma, Abubakar Wani, Prashant Joshi, Vikas Kumar, Santosh K Guru, Sonali S Bharate, Shashi Bhushan, Ram A Vishwakarma, Ajay Kumar, Sandip B Bharate	Discovery of a marine-derived bis-indole alkaloid fascaplysin, as a new class of potent P-glycoprotein inducer and establishment of its structure-activity relationship.	European Journal of Medicinal Chemistry 11/2015; 107:1-11., DOI:10.1016/j.ejmech.2015.10.049
Santosh Kumar Guru, Anup Singh Pathania, Suresh Kumar, Deshidi Ramesh, Manjeet Kumar, Satiander Rana, Ajay Kumar, Fayaz Malik, P. R. Sharma, B. K. Chandan, Sundeep Jaglan, J. P. Sharma, Bhahwal Ali Shah, Sheikh Abdullah Tasduq, Surrinder K Lattoo, Abdul Faruk, A. K. Saxena, R. A. Vishwakarma, Shashi Bhushan:	Secalonic Acid-D represses HIF1α/VEGF-mediated angiogenesis by regulating the Akt/mTOR/p70S6K signaling cascade.	Cancer Research 05/2015; 14(14)., DOI:10.1158/0008-5472.CAN-14-2312
Jaideep B Bharate, Yazan S Batarseh, Abubakar Wani, Sadhana Sharma, Ram A Vishwakarma, Amal Kaddoumi, Ajay Kumar, Sandip B Bharate	Synthesis and P-glycoprotein induction activity of colupulone analogs.	Organic & Biomolecular Chemistry 05/2015; 13(19):5488-96., DOI:10.1039/c5ob00554j
Anup S Pathania, Zahoor A Wani, Santosh K Guru, Suresh Kumar, Shashi Bhushan, Ajay Kumar, Fayaz Malik:	The anti-angiogenic and cytotoxic effects of the boswellic acid analog BA145 are potentiated by autophagy inhibitors.	Molecular Cancer 01/2015; 14(1)., DOI:10.1186/1476-4598-14-6
Anup S Pathania, Amit Joshi, Suresh Kumar, Santosh K Guru, Shashi Bhushan, Parduman R Sharma, Wajid W Bhat, Ajit K Saxena, Jaswant Singh, Bhahwal A Shah, Samar S Andotra, Subhash C Taneja, Fayaz A Malik, and Ajay Kumar.	Reversal of boswellic acid analog BA145 induced caspase dependent apoptosis by PI3K inhibitor LY294002 and MEK inhibitor PD98059.	Apoptosis 08/2013; 18(12)., DOI:10.1007/s10495-013-0889-4
Suresh Kumar, Ajay Kumar, Anup Singh Pathania, Santosh Kumar Guru, Srinivas Jada, Parduman Raj Sharma, Shashi Bhushan, Ajit Kumar Saxena, H M Sampath Kumar, Fayaz Malik.	Tiron and trolox potentiate the autophagic cell death induced by magnolol analog Ery5 by activation of Bax in HL-60 cells.	Apoptosis 03/2013; 18(5)., DOI:10.1007/s10495-013-0805-y

Patents

Author Contributors	Inventors/ Contributors	Title	Description	Year
Sandip Bharate, Ajay Kumar, Jaideep Bharate, Prashant Joshi, Abubakar Wani, Ramesh Mudududdla, Rohit Sharma, Ram Vishwakarma	Polyprenylated phloroglucinol compounds as potent P- glycoprotein inducers.	US Patent Number: US 10,202,326 B2.	Date of Patent: Feb 12, 2019.
Bharate Sandip, Kumar Ajay, Manda Sudhakar, Joshi Prashant, Bharate Sonali, Wani Abubakar, Sharma Sadhana, Vishwakarma Ram.	Alkylidene Phosphonate esters as P-glycoprotein inducers.	US Patent number: US 10 , 377 , 781 B2.	Date of Patent: Aug 13 , 2019.
Vishwakarma Ram, Bharate Sandip Bibishan, Kumar Ajay, Singh Baljinder, Kumar Ashok, Bhushan Shashi, Hamid Abid, Joshi Prashant, Guru Santosh Kumar, Kumar Suresh, Hussain Aashiq, Qazi Asif Khurshid, Bharate Sonali Sandip, Sharma Parduman, Saxena Ajit Kumar, Mondhe Dilip Manikrao, Mahajan Girish, Wani Zahoor	10 Substituted colchicinoids as potent anticancer agents.	US Patent Number: US 9 , 868 , 695 B2.	Date of Patent: Jan 16, 2018
Bharate Sandip, Kumar Ajay, Manda Sudhakar, Joshi Prashant, Bharate Sonali, Vishwakarma Ram.	N-Substituted beta-carbolinium compounds as potent P-glycoprotein inducers.	US Patent Number: US 10,072,009 B2.	Date of Patent Sep 11. 2018.
Vishwakarma RA, Kumar A, Khan IA, Bharate SB, Joshi P, Singh S, Satti N.	A pharmaceutical composition for the treatment of multi-drug resistant infections	Granted in EP – EP15807704.0 US patent publication number US20170273939A1	Nov 28, 2018
Ajay Kumar, Inshad Ali Khan, Surrinder Koul, Pyare Lal Sangwan, Dilip M Mondhe, Utpal Nandi, Gurdarshan Singh, Manoj Kumar Tikoo, Sadhana Sharma, Abubakar Wani, Santosh Kumar Rath, Samsher Singh, Mubashir Javeed Mintoo, Ram A Vishwakarma	Pharmaceutical compositions to enhance the bioavailability/bioefficacy of drugs.	IN 201911047260	2020
Qazi G N, Taneja S C, Singh J, Saxena A K, Sethi V K, Mondhe D M, Kapahi B K, Bhushan S, Andotra S S, Shah B, Singh S, Pal H C, Malik F, Kumar A, Sharma M.	A pharmaceutical composition for the treatment of cancer and related disorders.	Indian Patent Number: 268507	dated 31-08-2015
Bharate SS, Singh R, Gupta M, Singh B, Katare AK, Kumar A, Bharate SB, Vishwakarma RA.	Gastroretentive sustained release formulations of Bergenia ciliata.	IN201711036683; WO2019077620A1	2019
Bharate SS, Kumar V, Gupta M, Gandhi S, Kumar A, Bharate SB, Vishwakarma RA..	Sustained release formulations of Dysoxylum binectariferum	IN201811014818, WO2019202610A1	2019
Bharate SS, Kumar V, Singh R, Rani S, Gupta M, Kumar A, Bharate SB, Vishwakarma RA.	Sustained release formulations of Crocus sativus	IN201711036084, WO2019077621A1	2019

Awards / Honours

Awards and Honours

CSIR-Senior Research Associate Fellowship (2013)
CSIR-Research Associate Fellowship (2010)
Postdoc Fellowship, University of South Alabama, USA (2010)
CSIR-Junior Research Fellowship (2004)
UGC-Junior Research Fellowship (2004)

Group

Students

Photo	Name	Area of Interest	Position
	Mohd Fareed	His work is focused on exploring the genetic diseases, using the next-generation sequencing (NGS) platform. His ongoing research plans include deaf-mute syndrome (hearing loss), chronic kidney disease (CKD), acute lymphoblastic leukemia and rare genetic disorders among the population of Jammu & Kashmir. He is also engaged in CSIR-IIIM cell lines authentication using genetic STR markers.	Dr. Mohd Fareed (PhD) is engaged as DST-INSPIRE faculty (AcSIR Assistant Professor) at CSIR-IIIM.
	Mehboob Ali	He is trying to understand the complex relationship between autophagy and inflammasome mediated inflammation. He has identified some small molecules, which can help to decipher the talk between Autophagy and NLRP3 inflammasome.	Mehboob Ali is a Senior Research Fellow.
	Ankita Sharma	Her Ph.D. work is focused primarily on clearance of protein aggregates by using pharmacological activation of proteolytic mechanisms in the brain.	Ankita Sharma is a Senior Research Fellow.
	Sushil Choudhary	His research is focused on brain aging and related diseases. He is trying to comprehend if the brain aging can be slowed to delay the onset of pathological changes in brain.	Sushil Choudhary is a Senior Research Fellow.
	Dilpreet Kour	Her research interests include simultaneous targeting of two important facets of neurodegeneration; Autophagy and Inflammation.	Dilpreet Kour is a Senior Research Fellow.
	Lakhvinder Singh	Fellow. He is trying to understand if the age-related defects in autophagy can be corrected pharmacologically.	Lakhvinder Singh is a Junior Research