Pravin Kumar Jha

EDUCATION

PhD, M.S.(Pharm)

RESEARCH INTERESTS

Biotechnology, Peptide Synthesis, Pharmacy

Scopus Publications

DNA polymerase β of Leishmania donovani is important for infectivity and it protects the parasite against oxidative damage
Mohd. Imran Khan, Anshul Mishra, Pravin K. Jha, Kumar Abhishek, Rachna Chaba, et al.
International Journal of Biological Macromolecules, 2019
Vicinal abasic site impaired processing of a Tg:G mismatch and 8-oxoguanine lesions in three-component bistranded clustered DNA damage
Bhavini Kumari, Pravin Jha, Kislay K. Sinha, Prolay Das
Rsc Advances, 2018
The occurrence of 7,8-dihydro-8-oxo-2′deoxyguanosine (8-oxodG), thymine glycol:guanine (Tg:G) mismatch and abasic site DNA damage lesions in close proximity induce repair refractive non-DSB cluster.
Oxidative stress-mediated overexpression of uracil DNA glycosylase in Leishmania donovani confers tolerance against antileishmanial drugs
Anshul Mishra, Mohd. Imran Khan, Pravin K. Jha, Ajay Kumar, Sushmita Das, et al.
Oxidative Medicine and Cellular Longevity, 2018
Leishmania donovaniis an intracellular protozoan parasite that causes endemic tropical disease visceral leishmaniasis (VL). Present drugs used against this fatal disease are facing resistance and toxicity issues. Survival of leishmania inside the host cells depends on the parasite’s capacity to cope up with highly oxidative environment. Base excision repair (BER) pathway inL. donovaniremains unexplored. We studied uracil DNA glycosylase (UNG), the key enzyme involved in BER pathway, and found that the glycosylase activity of recombinant LdUNG (Leishmania donovaniUNG) expressed inE. coliis in sync with the activity of the parasite lysate under different reaction conditions. Overexpression of UNG in the parasite enhances its tolerance towards various agents which produce reactive oxygen species (ROS) and shows a higher infectivity in macrophages. Surprisingly, exposure of parasite to amphotericin B and sodium antimony gluconate upregulates the expression of UNG. Further, we found that the drug resistant parasites isolated from VL patients show higher expression of UNG. Mechanisms of action of some currently used drugs include accumulation of ROS. Our findings strongly suggest that targeting LdUNG would be an attractive therapeutic strategy as well as potential measure to tackle the problem of drug resistance in the treatment of leishmaniasis.
HAT2 mediates histone H4K4 acetylation and affects micrococcal nuclease sensitivity of chromatin in Leishmania donovani
Pravin K. Jha, Mohd. Imran Khan, Anshul Mishra, Pradeep Das, Kislay K. Sinha
Plos One, 2017
Histone post-translational modifications (PTMs) such as acetylation and methylation are known to affect chromatin higher order structures. Primary targets of these modifications include basic residues present at N-terminus tail region of core histones. Four histone acetyltransferase (HAT) genes have been identified in trypanosomatids. HAT1, HAT3 and HAT4 of Leishmania donovani have been partially characterized. However, there is no report about HAT2 of Leishmania donovani. Lysine residues present on the N-terminal tail of Leishmania donovani histone H4 are conserved in other trypanosomatids and humans. PTMs of lysines modulate various functions at chromatin level. The four histone acetyltransferases encoded in Leishmania genome were over-expressed to analyse their functional activity. All four HATs were found actively acetylating core histones H3/H4. Similar to L. donovani HAT3 and HAT4, HAT2 was found to be a member of MYST family protein and have SAS2 type domain. Over-expression of HAT2 significantly increases acetylation of H4K4. To analyse the effect of HAT2 over-expression on chromatin accessibility, micrococcal nuclease digestion assay was performed. MNase digestion resulted in a higher proportion of the mononucleosomes and dinucleosomes in HAT2 over-expressing cells as compared to WT L. donovani cells. Acetylation of lysine-4 neutralizes the amino terminal region of histone H4. This weakens its interaction with neighbouring nucleosomes and the linker DNA. HAT2 over-expression in L. donovani resulted in highly accessible chromatin suggesting chromatin decondensation. HAT2 may have an important role to play in global regulation of transcription in L. donovani. Better understanding of these epigenetic determinants of parasite would help in designing novel therapeutic strategies.
Plasma Gelsolin Level in HIV-1-Infected Patients: An Indicator of Disease Severity
Kislay Kumar Sinha, Nagesh Peddada, Pravin Kumar Jha, Anshul Mishra, Krishna Pandey, et al.
AIDS Research and Human Retroviruses, 2017
Plasma gelsolin (pGSN) is a multifunctional protein involved mainly in severing and clearing of actin filaments. Its level correlates with inflammation and several diseases making it a potential biomarker of diagnostic and prognostic values. The pGSN level in groups of treated and untreated HIV-1-infected Indian patients is investigated in this study. This study aims at investigating the levels of pGSN in HIV-1-infected patients across different age, sex, severity of disease, and treatment status. Blood samples of 213 patients were analyzed for CD4 counts by flow cytometry and pGSN was quantified by enzyme-linked immunosorbent assay (ELISA). The level of pGSN is significantly increased in HIV-1 infected patients (227.2 ± 54.3 μg/ml) compared to healthy volunteers (167.9 ± 61.8 μg/ml). The level correlates with CD4 cell counts as patients with lower CD4 counts showed higher pGSN levels and vice versa. Gender does not affect pGSN level; however, antiretroviral (ARV) treatment reduces pGSN toward normal. Within low CD4 cell count group, the untreated patients have 52% higher pGSN than healthy volunteers, whereas with treatment, the difference reduces to 24%. Similarly, high CD4 cell count (>350 cells/mm3) group of patients showed 44% increase in pGSN in untreated patients compared to 21% increase in treated patients. There is an upregulation of pGSN in HIV-1 infection and it is inversely correlated with CD4 cell counts. Treatment with ARV drugs decreases pGSN levels toward normal. The monitoring of pGSN level in HIV-1-infected patients could be an important indicator of severity of disease and recovery during treatment.
A quantum dot-MUC1 aptamer conjugate for targeted delivery of protoporphyrin IX and specific photokilling of cancer cells through ROS generation
Seema Singh, Pravin Jha, Vandana Singh, Kislay Sinha, Sahid Hussain, et al.
Integrative Biology United Kingdom, 2016
A prototype DNA assembled quantum dot-photosensitizer (PS) nanodevice for targeted delivery of PS drug.
Up regulation of A2B adenosine receptor on monocytes are crucially required for immune pathogenicity in Indian patients exposed to Leishmania donovani
Vijayamahantesh, Ajay Amit, Santosh Kumar, Manas R. Dikhit, Pravin K. Jha, et al.
Cytokine, 2016
l-Asparaginase as a new molecular target against leishmaniasis: insights into the mechanism of action and structure-based inhibitor design
Jasdeep Singh, Ankit Srivastava, Pravin Jha, Kislay K. Sinha, Bishwajit Kundu
Molecular Biosystems, 2015
l-Asparaginases belong to a family of amidohydrolases that catalyze the conversion of l-asparagine into l-aspartic acid and ammonia.

INDUSTRY EXPERIENCE

13 Years