Gopal P. Jadhav, PhD, Dr
Gopal P. Jadhav, Dr, PhD

Gopal P. Jadhav, Dr, PhD

Assistant Professor
Board Membership, Creighton University, Health ans Safety - Serving as a member on a sub-committee of the Laboratory Safety Committee to evaluate software for maintaining and reporting chemical inventory at Creighton.
School of Medicine

Expertise/Specializations

  • Synthetic organic chemistry: Hands on experience in modern synthetic organic chemistry like multi-step syntheses of drug like molecules, heterocycles, peptides, etc., parallel synthesis using Radley’s. Independent planning and execution of SAR.
  • Analytical techniques: Hands on modern separations techniques. Adept at using NMR, HPLC (analytical, prep., normal, RP, ion-exchange, size-exclusion), GC-, LC-MS, UV/VIS, IR, CD, detection based on fluorescence.
  • Hands on Molecular modelling softwares: Schrodinger Maestro (GLIDE, Homology Modeling, Epik, Ligprep, Protprep) Sybyl7.3, 8.0, Pymol, Database search (Zinc) and processing, Docking (GOLD, Glide, Openeye), Homology modelling, SciFinder, Beilstein, MDL/ISIS
  • Bioassay techniques: Advanced skills in Splenocyte proliferation assays in murine leukocytes and human blood monocytes (immune assay) and Bioluminescence induction assay using luminometer (microbiological assay).

Academic Appointments

Department

  • Pharmacology and Neuroscience

Position

  • Assistant Professor

Teaching Activity

  • CTS 719 (Fall 2017) DRUG DISCOVERY AND TRANSLATION OF RESEARCH INNOVATION TO COMMERCIAL ENTITIES: ACADEMIC ENTREPRENEURSHIP (3)

Biography

After obtaining a Bachelor and Masters degrees in pharmacy from the Pune University (India) in 1998, Dr Gopal spent a year working as a synthetic chemist and three years working as Lecturer of Medicinal chemistry in India, before undertaking a PhD at the University of Nottingham, UK. He completed Ph D under the supervision of Dr S R Chhabra, Prof. Peter Fischer, Prof. David Pritchard and Prof. Barrie Kellam and  continued to work for five years as post-doctoral research fellow on following projects.
1) Cancer Research project funded by BBSRC, UK, focusing on the work involving Computer aided designing and synthesis of small chemical molecules as inhibitors of pRb-E7 interactions. 

2) Seeding Drug Discovery project funded by Wellcome Trust, UK focusing on the Synthesis of novel chemicals and lead optimization of new highly selective beta-blockers in the management of cardiovascular disorders.

3) project funded by MRC, UK, focusing on Development of Inhibitors of Human deadnylase enzyme, new treatment for the Osteoporosis.

Subsequently, Dr Gopal spent one and a half years as a senior research scientist at the RD Alternative Discovery & Development, GlaxoSmithKline (Madrid Trescants, Spain) where he worked on collaborative-project with Prof. Michael Pollastri (Northeastern University, USA) and Prof. Harry De Koning (University of Glasgow, UK), involving structural optimization of GSK675728A, hPDE4 inhibitor to generate novel pharmacophore(s) as potent TbrPDE1 inhibitors that are selective over hPDEs in the management of African sleeping sickness (CNS disorder). 
Dr Gopal joined Creighton University in June 2016 as Postdoctoral research fellow and promoted to Assistant Professor of medicinal chemistry in early 2017. He is working as assistant professor within the school of Medicine under the leadership of Dr Peter Abel.

Publications and Presentations

Articles

  • Book chapter entitled "Laser Technology to facilitate Drug Discovery and Development Processes; Perspective to recent advancements",  Advances in Laser and Optic research, Laser therapies -Types, uses and safety; Chapter 10; Jan 2020
    Authors: Shantanu Hati and *Gopal P. Jadhav
    *Gopal Jadhav@creighton.edu
    https://novapublishers.com/shop/laser-therapies-types-uses-and-safety/
     , Nova Science, Chapter 10, 237-250, 2020
  • Article ID: FEB412605
    Article DOI: 10.1002/2211-5463.12605
    Internal Article ID: 16393586
    Article: 1-Hydroxy-xanthine derivatives inhibit the human Caf1 nuclease and Caf1-containing nuclease complexes via Mg2+-dependent binding
    Journal: FEBS Open Bio
    Congratulations on the acceptance of your article for publication in FEBS Open Bio.
    https://doi.org/10.1002/2211-5463.12605

    Abstract:
    In eukaryotic cells, cytoplasmic mRNA is characterised by a 3’poly(A) tail. The shortening and removal of poly(A) tails(deadenylation) by the Ccr4-Not nuclease complex leads to reduced translational efficiency and RNA degradation.Using recombinant human Caf1 (CNOT7) enzyme as a screening tool, we recently described the discovery and synthesis of a series of substituted 1-hydroxy-3,7-dihydro-1H-purine-2,6-diones(1-hydroxy-xanthines) as inhibitors of the Caf1 catalytic subunit of the Ccr4-Not complex. Here, we used a chemiluminescence-based AMP detection assay to show that active 1-hydroxy-xanthines inhibit both isolated Caf1 enzyme and human Caf1-containing complexes that also contain the second nuclease subunit Ccr4(CNOT6L)to a similar extent,indicating that the active site of the Caf1 nuclease subunit does not undergo substantial conformational change when bound to other Ccr4-Not subunits. Using differential scanning fluorimetry, we also show that binding of active 1-hydroxy-xanthinesrequiresthe presence of Mg2+ions, which are present in the active site of Caf1., FEBS Openbio, 2019
  • Rai V, Jadhav GP, Boosani CS. Annals Vasc Med Surg. 2019; 2(1): 1007

    Abstract
    Atherosclerosis is a chronic inflammatory disease of the vasculature that results in hardening of the vessel wall and narrowed lumen. Development of the atherosclerotic plaque starts from the deposition of the lipids in the fatty streak followed by its progression to atheroma, atheromatous plaque, and fibroatheroma. Diabetes mellitus (hyperglycemia), hypertension, smoking, obesity (hypercholesterolemia, dyslipidemia), male sex, family history of atherosclerosis, or genetic susceptibility are the risk factors for atherosclerosis. Chronic inflammation, immune cells infiltration, a bacterial or viral infection of the plaque, intraplaque hemorrhage, and endothelial and vascular smooth muscle dys regulation renders a stable plaque (rich in VSMC and collagen with few inflammatory cells) unstable (few VSMCs, more macrophages, and less collagen) which are prone to rupture. The role of various mediators of inflammation (damage associated molecular proteins), pro inflammatory cytokines (interleukin-1β, -6, -8, tumor necrosis factor-α etc.), and surface receptors (triggering receptors expressed on myeloid cell 1, Toll-like receptors, receptor for glycation end products etc.) in the pathogenesis of plaque development and rupture has been discussed in the literature. The mechanistic aspects of plaque progression have been discussed mainly at the protein level. The epigenetic regulation of atherosclerosis is a current area of interest to researchers. However, regulation of the development, progression, and rupture of the atherosclerotic plaque at the transcriptional level has not been studied in detail. This review emphasizes the role of transcription factors associated with atherosclerotic plaque progression and rupture.
    http://www.remedypublications.com/annals-of-vascular-medicine/articles/pdfs_folder/avms-v2-id1007.pdf, Annals of Vascular Medicine & Surgery, 2 (1), 1007, 2019
  • TREM-1; Is It a Pivotal Target for Cardiovascular Diseases?
    by Kouassi T. Kouassi,Palanikumar Gunasekar,Devendra K. Agrawal andGopal P. Jadhav
    J. Cardiovasc. Dev. Dis. 20185(3), 45; https://doi.org/10.3390/jcdd5030045 (registering DOI) - 7 September 2018
    Abstract 
    Cardiovascular diseases (CVDs) are as menacing as ever and still continue to kill adults worldwide, notwithstanding tremendous efforts to decrease their consequent mortality and morbidity. Lately, a growing body of research indicated that inflammation plays a pivotal role in the pathogenesis and complications of CVDs. A receptor of the immunoglobulin superfamily, triggering receptors expressed on myeloid cells-1 (TREM-1) was shown to induce and amplify the inflammation in both acute and chronic disease’ pathogenesis and progression, which hence makes it one of the most important complication factors of CVDs. Thus, studies endeavored to investigate the role played by TREM-1 in CVDs with respect to their etiologies, complications, and possible therapeutics. We examined here, for the first time, the most relevant studies regarding TREM-1 involvement in CVDs. We critically analyzed and summarized our findings and made some suggestions for furtherance of the investigations with the aim to utilize TREM-1 and its pathways for diagnostic, management, and prognosis of CVDs. Overall, TREM-1 was found to be involved in the pathogenesis of acute and chronic cardiovascular conditions, such as acute myocardial infarction (AMI) and atherosclerosis. Although most therapeutic approaches are yet to be elucidated, our present research outcome displays a promising future to utilizing the TREM-1 pathway as a potential target for understanding and managing CVDs
     , Journal of Cardiovascular Development and Disease — Open Access Journal, 5 (3), 45, 2018
  • Jitendra D. Bhosale 1,Rajesh Dabur 2,Gopal P. Jadhav 3,*  andR. S. Bendre 1,* 
    1 School of Chemical Sciences, North Maharashtra University, Jalgaon 425001, India
    2 Department of Biochemistry, Maharshi Dayanand University, Rohtak 124001, India
    3 School of Medicine, Department of clinical & translational sciences, Creighton University, Omaha, NE 68178, USA
    * Authors to whom correspondence should be addressed.

    https://www.ncbi.nlm.nih.gov/pubmed/29641457
     , Molecules, 23 (4), 875, 2018
  • Jillian G Baker, Sheila M Gardiner, Jeanette Woolard, Christophe Fromont, Gopal P Jadhav, Shailesh Mistry, Kevin SJ Thompson, Barrie Kellam, Stephen J Hill, Peter M Fischer; Novel selective β1-adrenoceptor antagonists for concomitant cardiovascular and respiratory disease; FASEB J. 31, 000–000 (2017). www.fasebj.org, FASEB Journal, 31, 2017
  • Murray Ewan, Crowley Rebecca, Truman Alex, Clarke Simon, Cottam James, Jadhav Gopal, O'Shea Paul, Lindholm Catharina, Cockayne Alan, Chan Weng, Chhabra Siri, Williams Paul; Targeting Staphylococcus aureus Quorum Sensing with Non-Peptidic Small Molecule Inhibitors J. Med. Chem., 2014, 57 (6), pp 2813–2819, Journal of Medicinal Chemistry, 57(6), 2813-2819, 2014
  • Maryati Maryati, Ishwinder Kaur, Gopal P. Jadhav, Loyin Olotu-Umoren, Blessing Oveh, Lubna Hashmi, Peter M. Fischer and G. Sebastiaan Winkler*, Nucleic Acids Research, 42(5), 1–10, 2013
  • Gopal P. Jadhav, Siri Ram Chhabra, Gary Telford, Doreen S. W. Hooi, Karima Righetti, Paul Williams, Barrie Kellam, David I. Pritchard, and Peter M. Fischer ; Immunosuppressive but Non-LasR-Inducing Analogues of the Pseudomonas aeruginosa Quorum-Sensing Molecule N-(3- Oxododecanoyl)-L-homoserine Lactone ; J. Med. Chem. 2011, 54, 3348– 3359;, Journal of Medicinal Chemistry, 54, 3348– 3359, 2011
  • *Gopal P. Jadhav; Tanya Ray H. N. More; K. R. Mahadik and A. D. Deshpande; Estimation of Piroxicam beta cyclodextrin by High Performance Liquid Chromatography from marketed formulations; Indian Drugs;, Indian Drugs, 36(8), 505-508, 1999
  • *Gopal P. Jadhav; Tanya Ray H. N. More; K. R. Mahadik and A. D. Deshpande; Estimation of Piroxicam beta cyclodextrin by High Performance Liquid Chromatography from marketed formulations; Indian Drugs, Indian Drugs, 36(8), 505-508, 1999
  • Gopal P. Jadhav; H. N. More, K. R. Mahadik ; Simultaneous estimation of Nalidixic acid and Metronidazole using UV/Visible spectrophotometer; Indian Drugs; , Indian Drugs, 35(8), 475-480, 1998
  • Author(s): G. P Jadhav, H. N More, K. R Mahadik
    A simple, rapid, economical and reproducible method has been developed for simultaneous estimation of nalidixic acid and metronidazole from pharmaceutical formulations using multicomponent mode of Jasco V-530 UV/VIS spectrophotometer. Wavelength range between 400 to 220 nm was used for estimated of both drugs. For analysis, six mixed standards were used. The results were confirmed by recovery studies and statistical evaluation. The method requires no manual calculations.
    http://www.ijpsonline.com/articles/simultaneous-uvspectrophotometric-estimation-of-nalidixic-acid-and-metronidazole-from-various-multicomponent-formulation.pdf, Indian Journal of Pharmaceutical Sciences, 60(4), 246-248, 1998
  • *A. D. Kale, S. J. Kachhwaha, Gopal P. Jadhav and Piyush Trivedi; Spectrophotometric estimation of Dicyclomine hydrochloride from combined dosage forms by ion pair complex; Indian Drugs, Indian Drugs, 35(11), 718-720

Editing and Reviews

  • Surface Plasmon Resonance, Orbitrap mass spec and Raman advancements: Exciting new techniques in drug Discovery; Editorial (Invited)
    Gopal Jadhav, Pavan Prathipati, Harsh Chauhan, Expert Opinion on Drug Discovery

Presentations

  • Invited talk on " The development of selective Beta 1adrenergic receptor inhibitors for the management of Cardiovascular diseases".
    Venue: SGMSPM's Dnyanvilas College of Pharmacy, Pune, India.
    https://www.dvcop.com
     , 2018
  • Invited talk on "TREM-1 drug discovery, a pivotal target for Cardiovascular disorders"
    Venue: STES's Sinhgad College of Pharmacy, Pune, India.
    www.sinhgad.edu, 2018

Research and Scholarship

Research and Scholarship Interests

  • Drug discovery in Cardiac and cardiovascular disorders
    Drug discovery in immuno and inflammatory disorders
    Drug discovery in Quorum sensing
    Drug discovery in Highly neglected diseases
     

Current Research Projects

  • Dr. Jadhav is working on the design and development of novel inhibitors of triggering receptor expressed on myeloid cells–1 (TREM-1), in the management of life threatening sepsis and CVD. This interdisciplinary research warrants use of computer aided drug design approach to develop and synthesis of small drug like molecules. Current inhibitors are peptide molecules (LR-17 and LR-12), that have a very short half-life and possibly with multiple targets.

    Molecular docking and HTS assay techniques will be employed to identify from from a library of 80000 diverse chemical molecules. These hits will be tested for TREM-1 inhibitory potential to identify new chemical lead(s). Lead(s) will be recruited for extensive chemical modifications (SAR- development) in order to optimize potency, toxicity and druggability.  

Grant Funding Received

  • Development of small chemical-molecule inhibitors of quorum sensing regulator: a novel treatment for antibiotic resistant bacterial infections. (NIH-R21-Resubmitted)
  • Project title: A high-throughput multi-user Biacore surface plasmon resonance system for studying biomolecular and biochemical interactions. Description: The grant will allow us to procure Biacore SPR 8K instrument. This instrument will be utilized to evaluate interaction between Novel GPJ small molecules and target receptors such as TREM1 for cardiovascular studies and MvfR for anti antibiotic resistant. This instrument will be available to other investigators as a core instrument. Role: Co-Investigator.
  • New Therapeutic Targets and Agents to Treat Therapy-resistant (Refractory) Asthma My role: Characterization of PFD derivative CXN-8 as a p63RhoGEF inhibitor and potent bronchodilator Co-investigator, I am a medicinal chemist and has many years of experience using molecular docking analysis to identify the putative interaction sites of small molecules and their targets. I will work with the graduate student to characterize CXN-8 and p63RhoGEF interaction (Aim 1.3) and provides advice and assistance to develop more potent pirfenidone derivatives to inhibit p63RhoGEF function.

Awards and Honors

  • Novel Ether Linked Compounds and Improved Treatments for Cardiac and Cardiovascular Disease, 2012
  • Novel Cyclic Phenoxy Compounds and Improved Treatments for Cardiac and Cardiovascular Disease, 2015
  • PHENOXYPROPANOL DERIVATIVES AND THEIR USE IN TREATING CARDIAC AND CARDIOVASCULAR DISEASES, 2012
  • , 2019