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Dr. Kshitish Acharya

Background: Dr. Kshitish K Acharya completed most of his basic education within Karnataka and worked in a wild life research project for one year in Western Ghats after his MSc in Zoology. With support from CSIR (NET-JRF & SRF), he conducted behavioral, physiological, and endocrinological experiments to study the pheromonal influences on implantation in mice, during his doctoral work (1990-96, BHU, Varanasi). He continued working in the field of reproductive biology during his post-doctoral research work, extensively using molecular biology / cell-culture techniques in the Indian Institute of Science (IISc), Bengaluru (~2 years) and University of Virginia, Charlottesville, USA (~ 4 years). He then worked in a biotech company as the head of the research as well as production unit for one year, before joining IBAB in March 2003. He  intends to use an integrated approach of molecular biology techniques, including cloning and expression of proteins, and computational approaches, to generate knowledge that can assist detecting and curing this disorder. Such a knowledge can also promote research towards development of better male contraceptives, which are required for countries such as India. His team is currently exploring the transcriptome of clinical testis samples from NOA-donors via Next Generation Sequencing (NGS), and characterizing some of the proteins involved in spermatogenesis and/or meiosis in general.

RESEARCH:

Main research interest: Understanding the transcriptional regulatory mechanisms in the mammalian tissues can help not only to establish the molecular details associated with various tissue-specific conditions, but also to identify better targets for research towards diagnostics, prognostics and therapeutics of diseases affecting different tissues. With this thought, Dr. Kshitish is exploring the transcriptome of human testis tissue with a particular focus on a type of male infertility called Non-Obstructive Azoospermia (NOA). He  intends to generate knowledge that can assist detecting and curing this disorder, as well as promote research towards development of better male contraceptives, which is required for countries such as India. His team is currently exploring the transcriptome of clinical testis samples from NOA-donors via Next Generation Sequencing (NGS).

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NGS-based transcriptome profiling of testis biopsy samples from Indian NOA-donors has been performed. Dr. Kshitish also intends to compile public data from microarray and RNA-seq studies, for NOA as well as other relevant conditions in human testis. He intends to short-list most important transcripts for NOA condition by RNA-seq experiments and then explore the molecular interactions holistically by combining with every other data such as the ncRNA and CHIP data, available for the human testis. Potential marker-transcripts shall be further tested with individual gene-specific studies via RT-PCR & qRT-PCR. Novel mRNA-isoforms of significance shall be cloned, expressed and corresponding proteins characterized in due course.

At a broader level, Dr. Kshitish’s group is trying to first establish and complete the ‘molecular portrait’ of the mammalian testis tissue, including the transcriptional regulatory network.

They began by attempts to make a better use of already available gene expression data. Dr. Kshitish believes that, for most biological research today, it is very important to make an apt selection and use of biological databases and software. His team quickly realized the limitations in the existing gene expression databases, and hence first developed tissue-specific gene expression databases by painstakingly compiling the necessary data (via biocuration). Efforts have also been made by his team, in collaboration with ‘Shodhaka’, to list and compare biological databases and software (www.startbioinfo.com) so that an objective selection of tools/databases can be done, among all available resources, when needed. His team has been systematically comparing the bioinformatic resources for various applications such as data mining/literature search (Nature Precedings, 2011), protein-protein interactions, pathway analysis and non-coding RNA studies. In fact, they have identified lacunae in specific areas and developed new software for necessary final analysis of the transcriptomes. Tissue-specific gene expression databases (e.g., MGEx-Tdb & MGEx-Udb) have been developed. A few unique software have also been developed to analyze promoters (e.g., GREAM & MotDet) and perform experimental analysis/validation (Ex-ExPrimer). These steps carried out over the last 7 years as well as the novel meta data analysis methods (e.g., TIPMaP) and new normalization method for RNA-seq raw data would be used to derive highly refined sets of transcripts based on the similarity of their expression patterns. Such ground work and resources developed would also be of use to other researchers globally.

Other research interests: Dr. Kshitish is also interested in a few other research areas as indicated below:

  1. a) Genomic level analysis of flow of genetic information across human generations: The essence of genetics is to study the transfer of hereditary information across generations but this would be an unconceivable thought to pursue at the genomic level in humans – a decade back. But, now the NGS technology and associated reduction in cost and time has provided an excellent opportunity to address the human pedigree genomics. His team wishes to start a multi-generation genomic analysis of Indians.

He earlier contributed to a study plan to explore the genetic basis of the Handigodu disease via NGS. Recently, he has been involved in studying an important component of genetic information in human populations: the meiotic hotspot usage across generations. Owing to the interest and initiatives of an MSc student at IBAB, Mr. Manu S, his team has explored the global distribution of meiotic recombination sites in human chromosomes and their signature patterns. In collaboration with Dr. Thiyagarajan, they are currently trying to identify the molecular signature pattern of these hotspots.

b) Comparative analysis of regulatory networks of mammalian genes across tissues using reliable clusters of differently functioning mammalian promoters to,

  1. identify potential biomarkers for tissues and diseases, at the gene and transcript levels, and
  2. understand the molecular mechanisms associated with tissue-specific diseases, such as cancer.

Dr. Kshitish postulates that a holistic approach, currently  taken up for NOA, can enhance the chances of finding key genes for any disease. After completing the work with mammalian testis, the same work could be extrapolated to other tissues of interest – preferably in collaboration with other scientists.

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COLLABORATIONS: Dr. Kshitish is keen on collaborating with other scientists. His collaborators so far include scientists from other organizations such as the Kiwai MIO (Dr. Jayshree RS), NIRRH (Dr. Parte & Dr. Geetanjali S), Mumbai, Mysore University (Dr. Lalitha R), Mysuru, Mangalore University (Dr. Shashirekha), Mangaluru, ManipalAnkur hospital (Dr. Vasan S), Bengaluru, IISc (Dr. Utpal Nath), Bengaluru and Shodhaka Life Sciences Pvt. Ltd. (Bengaluru). Within IBAB, he currently collaborates with Dr. Srivatsan and Dr. Thiyagarajan.

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Following are some of the BIOINFORMATICS RESOURCES developed by Dr. Kshitish and his group:

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Please scroll-down or click here for a list of publications

TEACHING/TRAINING: Dr. Kshitish has been passionate about with specific objectives. He has been regularly teaching the following subjects as part of the post-graduate programs at IBAB: molecular biology, bioinformatics, as well as several allied subjects including basic biology and introductory GMPs and IPR. He has also conceptualized and developed unique novel courses – including a unique 14-months diploma to develop biotechnically reliable work force for industrial work as well as research in academia. He has successfully guided 2 PhD students: Mr. Darshan SC and Ms. Neelima Ch.

The unique Laboratory Course in Bio-Techniques (LCBT) developed and conducted by Dr. Kshitish, trained students in multiple aspects of research methodologies, mainly focusing on the abilities to perform molecular biology experiments. He convened 8 batches of LCBT successfully, and handled all activities to placements personally. The placement records (95%, across batches) and feedback from industry have been extremely positive for this program.

Dr. Kshitish has also designed and organized about 25 short-courses/workshops in wet-lab as well as data analysis sections. In addition, he has contributed to about 25 invited talks in different national/international conferences/seminars at various places, and taught complete courses as an adjunct professor/guest faculty at the MCOPS, Manipal (MTech course), CHG, Bengaluru (MSc course), IIIT (iMTech course) and JNCASR (PhD course work).  About 12 modular hands-on data analysis courses in the genomics, transcriptomics and proteomics, of 10 days’ duration, were successfully designed and conducted since 2009. These hands-on training sessions became very popular and form one of the most successful and earliest programs in the omics domain to be successfully conducted in India.

Examples of the short-courses organized by Dr. Kshitish K Acharya:

Modular training programs for biotechnology professionals in the industrially relevant areas such as fermentation, protein characterization, GMPs, GCPs and tech-transfer. October 2013- Feb 2014
One month modular course on genomics, transcriptomics & proteomics resources (with Shodhaka Life Sciences Pvt. Ltd.)  Sept 2008, June 2009 & May-June 2010
A prolonged course to train clinical practitioners in the area of advanced research methodologies (St. Johns research centre) 2010
10 days modular course on data analysis for genomics, transcriptomics & proteomics (mostly with Shodhaka Life Sciences Pvt. Ltd.) A popular program conducted more than a dozen times based on demand
A Lab-Course in Biotechniques  13 May -10 June, 2006
Mammalian Cell Culture  (theory and hands-on lab-sessions, with Hindustan Lever Ltd., Bengaluru & National Centre for Cell Sciences, Pune) 01 – 04 February 2006
Workshop for Sigma-Aldrich Chemicals Pvt. Ltd. (theory and hands-on lab-sessions) 21 – 22 December 2005
Recombinant DNA technology workshop (laboratory training) 04 – 23 June 2005
Introduction to Bioinformatics and Biotechnology 2004 & 2005
Recombinant DNA technology workshop (laboratory training) 20 – 25 March 2005
60 hour Cell and Molecular Course for the engineers/executives of Wipro-GE Health systems August – November 2003
5 day motivational and educational program for selected rural girls from different parts, at IBAB (as part of the Chetana program, an initiative of the ITBT, Government of Karnataka) 15-22 December 2017

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ENTREPRENEURSHIP: Dr. Kshitish founded a company (Shodhaka Life Sciences Pvt. Ltd., Bengaluru). Since 2009, ‘Shodhaka’ has been offering services to other scientists in the areas of biological data analysis, databases and software development, and biocuration. When needed the company has also offered bioinformatics-training for biologists.

 PhD STUDENTS:Darshan Mr. Darshan SC

Mr. Darshan SC recently completed PhD at IBAB. He mainly established expression-based gene clusters for prediction of mammalian promoters and expression patterns, and has published three papers (PLoS One. 2013;8(3):e58419; PLoS One. 2012;7(5):e36776. BMC Genomics. 2010 Aug 11;11:467).  He won the best poster award two international conferences. After BSc (Biotechnology, Zoology and Computer Science, 2005; DVS Arts & Science College, Shivamogga, Kuvempu University, Karnataka). He earlier completed MSc in Bioinformatics (2007, Jnana Sahyadri, Kuvempu University, Karnataka) with 2nd rank to the University, was selected at IBAB via a stringent selection before registering at Manipal University, Manipal for PhD. He is now a post doctoral fellow in a leading research group at the University of Alabama, USA

Neelima Ms. Neelima CH

Ms. Neelima Ch also recently completed her PhD at IBAB. She tried to understand differences in the preliminary stages of gene expression regulation in healthy and unhealthy mammalian tissues, and identify potential markers for some of the conditions. A part of her work helped to critically re-address microarray probe-qualities (BMC Genomics. 2010 Aug 11;11:467). After  BSc (Agriuculture, 2003; Acharya N.G Ranga Agricultural University, Baptala, Andhra Pradesh), she had completed MSc in bioinformatics (2006, SRM college, Madras university, Chennai, Tamilnadu). She qualified the written test and interview at IIIT, Hyderabad  and registered for PhD under the guidance of Dr. Kshitish Acharya K (IBAB, Bengaluru), and the co-guidance of Dr. Abhijit Mitra (IIIT, Hyderbad). She is currently taking a career break to address another crucial and happy phase of her personal life.

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PUBLICATIONS:

  1. Manu S, Acharya KK, Thiyagarajan S (2018) Systematic analyses of autosomal recombination rates from the 1000 genomes project uncovers the global recombination landscape in humans. bioRxiv PrePrint: https://www.biorxiv.org/content/early/2018/01/12/246702
  1. Adurthi S, Kumar MM, Vinodkumar HS, Mukherjee G, Krishnamurthy H, Acharya KK, Bafna UD, Uma DK, Abhishekh B, Sudhir Krishna, Parchure A, Murali A, and Jayshree RS (2017) Oestrogen Receptor-α binds the FOXP3 promoter and modulates regulatory T-cell function in human cervical cancer. Scientific Reports 7 7(1):17289.
  2. Narayanaswamy PB, Baral TK, Haller H, Dumler I, Acharya KK and Kiyan Y (2017) Transcriptomic pathway analysis of urokinase receptor silenced breast cancer cells: a microarray study. Oncotarget 8(60): 101572-101590.
  3. Kouser. K, P. G. Lavanya, Rangarajan L, K. Acharya KK (2016) Effective Feature Selection for Classification of Promoter Sequences. PLOS One 11(12): e0167165.
  4. Kumar MM, Davuluri S, Poojar S, Mukherjee G, Bajpai AK, Bafna UD, Devi UK, Kallur PP, Acharya KK, Jayshree RS. (2016) Role of estrogen receptor alpha in human cervical cancer-associated fibroblasts: a transcriptomic study. Tumour Biol. Apr;37(4): 4409-20.
  5. Pathak BR, Breed AA, Apte S, Acharya KK, Mahale SD. Cysteine-rich secretory protein 3 plays a role in prostate cancer cell invasion and affects expression of PSA and ANXA1. Mol Cell Biochem. 2016; 411(1-2):11-21.
  6. Chandrashekar DS, Dey P, Acharya KK (2015) GREAM: A web server to short-list the potentially important genomic repeat elements based on over-/under-representation in specific chromosomal locations such as the gene neighborhoods within or across 17 mammalian species. PLOS One Jul 24;10(7):e0133647.
  7. Kouser, Lalitha R, Chandrashekar DS, Acharya KK and Abraham EM (2015) Alignment Free Frequency Based Distance Measures for Promoter Sequence Comparison In: Bioinformatics and Biomedical Engineering Third International Conference, IWBBIO 2015, Granada, Spain, April 15-17, 2015. Proceedings, Part II;  Editors: Ortuño, Francisco, Rojas, Ignacio (Eds.) pp. 183-193, Springer.
  8. Prashanth Suravajhala and Kshitish Acharya. (2014) Whither genome sequencing of passer? Eur. Chem. Bull. 3(11), 1086-1087.
  9. Acharya KK (2014) Capacities vs. jobs in bioinformatics and biotechnology: a few points to the attention of current students & job-seekers In: “Biotech Career Ready Reckoner 2014” (BCRR 2014), Vivify Media Private Limited & Department of Biotechnology (DBT), Govt. of India. [free full text: http://www.shodhaka.com/pdf/CareerBioinfo_14_3_31.pdf.
  10. Bhagwat S, Dalvi V, Chandrasekhar DS, Matthew T, Acharya KK, Gajbhiye R, Kulkarni V, Sonawane S, Ghosalkar M, Parte P (2014) Acetylated alpha tubulin is reduced in individuals with poor sperm motilityFertility & Sterility101(1):95-104.e
  11. Roy D, Kumar V, Acharya KK, Thirumurugan K (2014) Probing the Binding of Syzygium-Derived alpha-Glucosidase Inhibitors with N- and C-Terminal Human Maltase Glucoamylase by Docking and Molecular Dynamics Simulation.Applied biochemistry and biotechnology  172(1):102-14
  12. Chitturi N, Balagannavar G, Chandrashekar DS, Abinaya S, Srini VS and Acharya KK (2013). TIPMaP: a web server to establish transcript isoform profiles from reliable microarray probes. BMC Genomics14: 922
  13. Bhagwat SR, Chandrashekar DS, Kakar R, Davuluri S, Bajpai AK, Nayak S, Bhutada S, Acharya KK, Sachdeva G (2013) Endometrial receptivity: a revisit to functional genomics studies on human endometrium and creation of HGEx-ERdbPLOS One8(3), e58419
  14. Bajpai, A.K., Davuluri, S., Chandrashekar, D. S., Ilakya, S., Dinakaran, M. and Acharya, K.K. (2012) MGEx-Udb: A Mammalian Uterus Database for Expression-Based Cataloguing of Genes across Conditions, Including Endometriosis and Cervical Cancer PLOS One 7(5), e36776
  15. Acharya KK, Chandrashekar DS, Chitturi N, Shah H, Malhotra V, Sreelakshmi KS, Deepti H, Bajpai A, Davuluri S, Bora P, Rao L. A novel tissue-specific meta-analysis approach for gene-expression predictions, initiated with a mammalian gene expression testis database. BMC Genomics, [2010]11: 467
  16. Kshitish K Acharya, Greta K & Harita H (2008) How do you choose your search engine(s)? Nature Precedings (pre-print; highly voted for) http://precedings.nature.com/documents/2101/version/2
  17. Kshitish K Acharya (2006). The Biotech-Bioinfo Interface in the Context of Education and Growth of the Biotechnology Industry in India Today. Biovistas 1: 7-13 (also at: http://www.shodhaka.com/pdf/Biovistas_manuscript_final.pdf)
  18. Kshitish K. Acharya, Chhabi K. Govind, Amy N. Shore, Mark H. Stoler, Prabhakara P. Reddi (2006) cis-Requirement for the Maintenance of Round Spermatid-Specific Transcription. Developmental Biology 15; 295(2):781-90.
  19. Sandhu KS and Kshitish K. Acharya (2005) ExPrimer: To design primers from exon-exon junctions. Bioinformatics 21(9):2091-2
  20. Sreekumar A, Acharya KK, Lalitha HS, India SS, and Seshagiri PB (2005). Germ cell-specific localization of immunoreactive riboflavin carrier protein in the male golden hamster: Appearance during spermatogenesis and role in sperm function. Reproduction  129(5):577-87.
  21. Reddi PP., Shore A., Shapiro JA, Anderson A, Stoler MH and Acharya KK and Herr JC (2003) Spermatid-specific promoter of the SP-10 gene functions as an insulator in somatic cells. Developmental Biology 262: 173-182.
  22. Reddi PP., Shore A., Acharya KK and Herr JC (2002) Transcriptional regulation of spermiogenesis: Insights from the study of SP-10 gene, which codes for an acrosomal protein. Journal of Reproductive Immunology 53: 25-36.
  23. Seshagiri P. B., Acharya, K.K., Jayaprakash, D., Satish, K.S. and Shetty, G (2002) Ovarian hyperstimulation in bonnet monkeys using gonadotrophins. In: Follicular Growth, Ovulation and Fertilization: Molecular and Clinical Basis. A. Kumar and A.K. Mukhopadhyay (Eds.).  Narosa Publishing House. New Delhi.
  24. Acharya KK, Roy A and Amitabh K. (1998) Relative role of olfactory cues and certain non-olfactory factors in foraging of fruit-eating bats. Behavioural Processes.  44(1): 59-64.
  25. Acharya KK and Dominic CJ (1997). Duration of the luteotrophic memory of the stud male odours formed in female mouse. J. Exp. Zool. 279: 626-632.

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CONSULTANCY:               

Dr. Kshitish has experience in certain industrial aspects of the life sciences sector, including management and organizational activities and is keen to be a consultant for

(a) specific research projects in biotechnology or bioinformatics organizations,

(b) training employees in specific areas including general professional skills, and

(c) setting molecular biology / cell culture laboratories

Examples of his consultancy are:

  • Wipro (in the area of microarray data analysis) and
  • Microtest Innovation (in the area of quality tests and stability studies of certain molecular products).
  • Scinnovation Consultants Pvt. Ltd. (selection and placement criteria in the biotechnology/bioinformatics area; 2005-2006)
  • A research group in a leading US University