Projects per year
Personal profile
Research interests
The major focus of Dr. Arun Sharma’s lab is the design and development of novel small drug-like molecules as potential cancer therapeutic and preventive agents, and testing them in various in vitro and in vivo cancer models.
This effort has resulted in the development of some potent anti-cancer agents and understanding of their efficacy, toxicity, pharmacokinetics, and mechanisms of action. The main strategies adapted for designing new agents include optimization of
- naturally occurring agents;
- existing drugs or agents that fail in clinical trials; and
- lead compounds obtained from chemical library screening, to enhance potency, bioavailability and therapeutic/chemopreventive index.
An example of natural product optimization includes the development of ISC-4, an isosteric selenium analog of isothiocyanates that occur naturally in cruciferous vegetables. ISC-4 was shown to be a PI3K/Akt pathway inhibitor that effectively inhibited tumor growth in melanoma and colon cancer xenograft models, alone and in combination with standard of care. Further optimization of ISC-4 structure has now led to a dual Akt pathway/topoisomerase II inhibitor NISC-6 as a potential melanoma therapeutic.
Through extensive structure-activity studies based on Selenium-NSAID hybrid molecules, Dr. Sharma’s lab has recently discovered two potent small molecules: Se-Aspirin, published recently and already commercially available; and AS-10, a bis-aspirinyl-selenazolidine analog which has shown great potential as a cancer therapeutic, particularly for pancreatic cancer. p-XS-Asp, another Se-aspirin hybrid molecule developed recently, is orally bioavailable and effective in preventing against NNK induced lung tumorigenesis.
Apart from developing anti-cancer compounds, Dr. Sharma’s lab is also focusing on developing "smart antibiotics." The emphasis is on designing and synthesizing cationic bolaamphiphiles (CABs) as carrier compounds that can transport antisense oligonucleotide (ASO) into C. difficile to selectively target the genetic material in C. difficile.
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
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Collaborations and top research areas from the last five years
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Targeting AR and AR-Variants in Castration-Resistant Prostate Cancer
Damodaran, C., Sharma, A. A. K. & Sharma, A.
2/1/21 → 1/31/24
Project: Research project
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A Novel Agent for Lung Cancer Prevention
Congressionally Directed Medical Research Programs
7/1/19 → 6/30/21
Project: Research project
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ISC-4 as a Novel Lung Cancer Chemopreventive Agent
Sharma, A. K. & Sharma, A.
9/30/09 → 8/31/10
Project: Research project
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Accumulation of Linoleic Acid by Altered Peroxisome Proliferator-Activated Receptor-α Signaling Is Associated with Age-Dependent Hepatocarcinogenesis in Ppara Transgenic Mice
Zhu, X., Liu, Q., Patterson, A. D., Sharma, A. K., Amin, S. G., Cohen, S. M., Gonzalez, F. J. & Peters, J. M., Aug 2023, In: Metabolites. 13, 8, 936.Research output: Contribution to journal › Article › peer-review
Open Access -
A small molecule inhibitor of Notch1 modulates stemness and suppresses breast cancer cell growth
Saran, U., Chandrasekaran, B., Tyagi, A., Shukla, V., Singh, A., Sharma, A. K. & Damodaran, C., 2023, In: Frontiers in Pharmacology. 14, 1150774.Research output: Contribution to journal › Article › peer-review
Open Access -
Corrigendum: A small molecule inhibitor of Notch1 modulates stemness and suppresses breast cancer cell growth (Frontiers in Pharmacology, (2023), 14, (1150774), 10.3389/fphar.2023.1150774)
Saran, U., Chandrasekaran, B., Tyagi, A., Shukla, V., Singh, A., Sharma, A. K. & Damodaran, C., 2023, In: Frontiers in Pharmacology. 14, 1207589.Research output: Contribution to journal › Comment/debate › peer-review
Open Access -
Cu-promoted synthesis of Indolo[2,3-b]quinoxaline-Mannich adducts via three-component reaction and their anti-proliferative evaluation on colorectal and ovarian cancer cells
Chowdhary, S., Raza, A., Seboletswe, P., Cele, N., Sharma, A. K., Singh, P. & Kumar, V., Mar 5 2023, In: Journal of Molecular Structure. 1275, 134627.Research output: Contribution to journal › Article › peer-review
2 Scopus citations -
Dissimilar effects of stereoisomers and racemic hydroxychloroquine on Ca2+ oscillations in human induced pluripotent stem cell-derived cardiomyocytes
Janicki, P. K., Singh, A., Sharma, A. K. & Ruiz-Velasco, V., Jul 2023, In: Physiological reports. 11, 14, e15760.Research output: Contribution to journal › Article › peer-review
Open Access
Prizes
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Outstanding Collaborative Research Team
Adair, James Hansell (Recipient), Amin, Shantu (Recipient), Claxton, David (Recipient), Desai, Dhimant (Recipient), Hengst, Jeremy (Recipient), Liao, Jiangang "Jason" (Recipient), Paulson, Robert (Recipient), Sharma, Arun (Recipient), Stanley, Bruce (Recipient), Wang, Hong-Gang (Recipient), Yun, Jong (Recipient) & Zhu, Junjia (Recipient), 2015
Prize