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Manish V.

Bais, DVM, PhD


R-205, 715 Albany Street
Boston MA 02118
Email: manish.bais11@gmail.com
https://www.bu.edu/orl/People.htm

CAREER GOAL:
To pursue career in industrial research. The specific interests are cell biology, musculoskeletal research, gene
therapy, peptide based delivery of siRNA and antibody, stem cell biology, genomics, siRNA, microRNA,
structure and function analysis, engineering of stem cell lines, animal models and basic cancer research.
EDUCATION:
Non-degree course: Boston University School of Medicine in Drug Discovery (2005).
Postdoctoral Fellow: Orthopedic Surgery lab, Boston University School of Medicine, Boston, MA (Sept 2004-
Present)
PhD: Animal Biotechnology, National Biotechnology Centre, Indian Veterinary Research Institute, Izatnagar,
India, 2004.
M.V.Sc.: Animal Biotechnology, National Biotechnology Centre, Indian Veterinary Research Institute,
Izatnagar, India, 2001.
D.V.M.: AVMA listed Nagpur Veterinary College, India, 1998.
PhD THESIS:
Identification of Novel Nuclear Localization Signal from IBD Virus for Development of Peptide Based
Delivery System
MVSc THESIS:
Sequence Analysis of Very Virulent Infectious Bursal Disease Virus of Poultry
PATENT:
Development of reagent for intracellular delivery of small molecule such as siRNA and antibody.
An Artificially Synthesized Peptide. Dr. Satish Kumar, Dr. Manish Virendrasingh Bais, Dr. Ranjit Singh
Kataria Dr. Mahendra Pal Yadav
Pub. No.: WO/2008/041047
International Application No: PCT/IB2006/002786
Publication Date: 10.04.2008
International Filing Date: 06.10.2006

POSITIONS AND DUTIES:


2004- present: Reader for thesis of 5 Master’s thesis submitted at BUMC, Boston, MA
2009- present: Manager In Vivo Imaging system for technical help
2004- present: Postdoctoral fellow in orthopaedic surgery, BUMC, Boston, MA
2001-2004 : Teaching assistant for Master’s and PhD students at National Biotechnology Center, India.
2001-2004 : As a mentor for scientific training program under NATP, Govt. of India project.
1998 : Internship in veterinary medicine at various animal hospitals.
RESERCH EXPERIENCE
Post-doc projects:
1. shRNA mediated knockdown of BMP2 in vitro and in vivo with lentiviral transduction particles:
Inhibition of BMP2 expression with lentiviral BMP2 shRNA prevented both mineralized nodule formation
in vitro and bone formation in vivo, and blocked the expression of Runx2 and osterix, transcriptional
determinants of terminal osteogenic differentiation. No effect was observed on the expression of Sox9, a
transcription factor expressed in committed chondroprogenitor and osteoprogenitor cells. Using antibodies
against CD146 and Sox9 immunohistological examination of the cell populations found in the medullary
space three days after bone marrow ablation showed qualitatively equal numbers of cells expressing these
skeletal progenitor and stem cell markers in control and BMP2 shRNA-treated animals. Cell sorting using
CD146 antibody showed similar quantitative results to the qualitative immunohistological findings. In
vitro studies showed that BMP7 rescued the expression of osterix and enhanced the expression of Sox9 but
had no effect on the expression of Runx2, while BMP2 rescued both Runx2 and osterix but did not enhance
the expression of Sox9. These results demonstrate that BMP2 is a central morphogenetic regulator of post
natal osteogenic differentiation but does not affect recruitment of cells to the osteoblastic lineage.
2. High Throughput Microarray Transcriptional Analysis of Fracture Healing and the Induction of
Embryonic Stem Cell-Related Genes:Bayesian modeling was used to generate the temporal profiles of
the transcriptome during fracture healing. The temporal relationships between ontologies related to
skeletogenesis, vasculogenesis, and neurogenesis were developed. The complement of all the expressed
BMPs, Wnts, FGFs, and their receptors were related to the subsets of transcriptional factors that were
concurrently expressed during fracture healing. We define during fracture healing the temporal patterns of
expression for 174 of the 193 genes known to be associated with human genetic skeletal disorders.
Approximately 300 of ~1000 known genes that are preferentially expressed in embryonic stem cells (ESCs)
showed induction. Nanog, one of the central epigenetic regulators associated with stem cell maintenance
was shown to be associated in multiple forms or bone repair as well as MSC differentiation. In summary,
these data present the first temporal analysis of the transcriptome of an endochondral bone formation
process that takes place during fracture healing. They show that neurogenesis is a predominant component
of skeletal tissue formation and suggest common pathways are shared between post natal stem cells and
those seen in ESCs.
3. Generation of Trangenic mouse models for studing bone diseases rheumatism, osteoporosis and bone
diseases:Inducible treansgenic mouse model generated by using novel Rapamycin based inducible system
has found to have stringent control over the gene regulation. Several lines of transgenic mouse such as
CMV driving chimeric transcription factor, inducible luciferase and inducible luciferase transgenic mice
were generated by pronuclear microinjection at transgenic core at Boston Medical Center. Different
components were bred together to make binary animals which could be induced by injecting diamerizing
agent AP21967 (derivative of Rapamycin which do not activate mTOR). Interestingly, fractures generated
in binary BMP2 inducible mice showed downregulation of ostoclast activity activity with elevation of
ostoblastic markes. Noggin and Trap5 were mainly downregulated. Micro-CT analysis showed slight
incrase in percent of bone formation.However, noninjured bones showed increased osteoclastic activity.
Histological and molecular analysis in progress to conclude exact uncerlysing mechanism by inducible
BMP2 expression. Another line of indicator animals, inducilbe luciferase animals showed acitivation of
luciferase in ex-vivo skin fibroblast culture and further being evaluated by IVIS luciferase system from
Xenogen. This study will evaluate the basic component and dose of drug for induction of particular gene
with Rapamycin based inducible system, identify the clinical therapeutic window needed for bone repair
with BMP2.
PhD projects:
4. Peptide forming liposome like structure, delivering biomolcules such as siRNA and
antibodies to cells: synthetic peptide idenitified from IBD virus named as Rath peptide (patented)
forms liposome like structre, deliver the small oligonucleotide such as siRNA or whole antibody
intracellular to cells by non-covalent interaction without any cytotoxicity. Interestingly, structural
and functional analysis showed that it forms self-aggregating nanoparticles withing range 10 to
150 nm range.
5. DNA vaccine for IBD to protect B cell response:Infectious Bursal disease virus of poulty destry bursa of
fabricious and affects the B cell population. Immunization of major antigenic VP2 gene overexpressed in
eukaryotic vector showed the protection of B cell population with challagne infection of IBDV.
6. New Castle Disease virus and induction of Apoptosis.
7. Bluetongue virus and induction of apoptotic pathway.
8. Sequencing and phylogenetic analysis of IBD virus.
9. Identification of T-helper and linear B epitopes for PPR disease diagnosis: Epitope mapping identified
T cell and B cell responsive synthetic peptide which were used to design ELISA assay for diagnosis of viral
infection such as PPR and Bursal disease.
Collaborative projects in post-doc:
10. shRNA mediated knockdown of Loxl2 in chondrogensis (PI: Trackman PC, BU dental school): Lox2
encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the
biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses
the first step in the formation of crosslinks in collagens and elastin. Apart from other roles of lox family
such as inhibition of prostate cancer cells, novel role of LoxL2 has been identified in chondrogenesis. Lox2
has been indentified in fracture callus. Lentivirus shRNA mediated knockdown shown to inhibit the
chondrogensis and downregulation of chondrogenic markers such as col2, sox9, aggrecan and Runx2.
11. Mechanotransduction and fracture repair (PI: Morgan E, BU school of Engineering):Fracture-healing
is regulated in part by mechanical factors. Study of the processes by which the mechanical environment of
a fracture modulates healing can yield new strategies for the treatment of bone injuries. In situ
hybridization in different comapartments with semiquantitave analysis the different regions in rat fractures
callus have been quatitated using riboprobes. This data along with molecular analysis in progress the hot
zones in fracture callus.
TECHNIQUES KNOWN
shRNA based knockdown in vitro and in vivo mouse model, Lentivirus gene therapy, Bioinformatics, Cell
Cultures, Real time PCR, Cloning and expression of gene, SDS-PAGE and Western blotting, Synthesis of
peptides and its Applications, Reverse Phase-HPLC, Fluorescence Microscopy, Gel Shift Assay, Serum
Protection Assay, DNAse Protection Assay, Circular Dichroism spectroscopy, Fluorescence spectroscopy,
Slot blot/ southern blot, Generation of transgenic construct, Genotyping of transgenic animals, Flow
cytometry, Experience on working with animal models such as bone marrow ablation model in mice and
animal immunization.
RESEARCH SUPPORT:
Ongoing Research Support
“Molecular Mechanisms of Skeletal Repair” (NIH funded)
Role: Post-doc
1P01-AR049920 Einhorn (PI), chairman orthopeadic surgery, Boston Medical Center
( 04/01/2004 - 09/31/2009 NIH)
AWARDS/HONORS:
• Recipient of University Merit-cum-means Scholarship throughout BVSc & AH degree program (1994-
1998).
• Awarded IVRI Junior Research Fellowship (JRF), sponsored by Indian Council of Agricultural Research
for MVSc (1999-2001).
• Recipient of IVRI Senior Research Fellowship (SRF), sponsored by Indian Council of Agricultural
Research for pursuing Ph.D (2001-2004).
PUBLICATIONS:
1. Bais MV, McLean J, Sabastiani P,Young M, Wigner N, Smith T, Kotton DN, Warman M, Einhorn TA,
Gerstenfeld LC Transcriptional Analysis Of Fracture Healing And The Induction Of Embryonic Stem Cell-
Related Genes During Fracture Healing. ( under revision to Plos One)
2. Bais MV, Wigner N, Young M, Toholka R, Graves DT, Morgan EF, Gerstenfeld LC and Einhorn TA BMP-
2 Is Essential for Post Natal Osteogenesis but not for Recruitment of Osteogenic Stem Cells (Manuscript
revised for Bone).
3. Ravindra P V, Tiwari AK, Ratta B, BaisMV, Chaturvedi U, Palia SK, Sharma B and Chauhan R S.Time-
course induction of Newcastle disease virus-induced extrinsic and intrinsic apoptotic pathways in infected
cells ( Submitted to BBRC)
4. Bais MV, Kumar S, Tiwari AK, Kataria RS, Nagaleekar VK, Shrivastava S, Chindera K. Novel Rath
peptide for intracellular delivery of protein and nucleic acids.Biochem Biophys Res Commun. 2008 May
23;370(1):27-32. Epub 2008 Mar 17. PMID: 18346454.
5. Nagaleekar VK, Tiwari AK, Kataria RS, Bais MV, Ravindra PV, Kumar S.Bluetongue virus induces
apoptosis in cultured mammalian cells by both caspase-dependent extrinsic and intrinsic apoptotic
pathways.Arch Virol. 2007;152(9):1751-6 PMID: 17530353
6. Bais MV, Kataria R.S, Tiwari AK, Viswas KN.,. Reddy AV, and Prasad N. Sequence analysis of an Indian
field isolate of infectious bursal disease virus shows six unique amino acid changes in the VP1 gene, Vet
Res Commun 28 (2004) 641-646. PMID: 15563111
7. Indervesh, Tiwari A. K., Kataria R. S.,. Viswas K. N, M. V. Bais, and Suryanarayana V. V., Isolates of
infectious bursal disease virus from India are of very virulent phenotype, Acta Virol 47 (2003) 173-177.
PMID: 14658846
8. Bais M. V.,. Kataria R. S,. Tiwari A. K, Indervesh, Suryanarayana V. V., and. Das S. K, Sequence analysis
of segment A of a field virus isolate from an outbreak of Infectious bursal disease in India, Acta Virol 47
(2003) 73-77. PMID: 14524472
9. Bais M.V.,. Tiwari A.K,. Kataria R.S, Indervesh and Das S.K. RT-PCR amplification and cloning of both
genome segments of an Indian infectious bursal disease virus. Indian J Poult Sci. (2003) 38 (1): 1-5.
10. Indervesh,. Kataria R.S. Tiwari A.K, and Bais M. V..and.Das S. K.. VP1 gene based RT-PCR/ restriction
enzyme analysis for the characterization of infectious bursal disease virus strains. Indian J poult sci.
(2002)37(2): 163-165.

ABSTRACTS:
1. Bais M V, Barnes GL, Gerstenfeld LC, Einhorn TA Loss of Osteogenic Differentiation by Knock- Down of
Endogenous BMP-2 Expression Can Be Rescued by the Exogenous Administration of BMP-7 and is
Mediated by Increased Osterix Activity. 54th Annual Meeting of the ORS March 2-5, 2008 San Franscisco,
CA
2. Bais M V., Wigner N., Young M., Toholka R., Graves D.,. Morgan E. F,. Gerstenfeld L. C,. Einhorn T. A
Dependence of Post Natal Osteogenic Differentiation on BMP2: Dissection of Osteogenic Lineage
Commitment by Lentivirus BMP2 shRNA ex vivo and in vivo. 30th ASBMR annual meeting Sept 12-16,
2008 Montreal, Canada
3. Bais MV, Mclean J, Sabastiani P, Young M, Smith T, Wigner N, Kotton DN, Einhorn TA, and
Gerstenfeld LC. Induction of embryonic stem cell-related pluripotency genes in in Post Natal Stem Cells
during Fracture Healing. 30th ASBMR annual meeting Sept 12-16, 2008 Montreal, Canada
4. Bais M.V,.Kataria R.S, Tiwari A. K, Indervesh,.Das S. K, and.Suryanarayana V. V.S. Sequence analysis of
segment A encoding polyprotein of field isolate of infectious bursal disease virus. Abstract presented at
IXth Annual conference of IAAVR and national Symposium on “concepts in Sustainable livestock
production and health in new Millennium (2002).”
5. Bais M.V, Satish Kumar,.Tiwari A.K, Kataria R.S.and.Viswas K.N “A peptide molecule, ‘Rath’, as a
machine to deliver oligonucleotide and antibody in the cells” (Abstract presentation at International
symphosia “Molecules, Machines and Network” from January 6-9, 2004 at Banglore, India).

6. Bais M.V, Satish Kumar,.Tiwari A.K,.Kataria R.S and.Viswas K.N “Designing a peptide vector for
transfection of plasmid in mammalian cells” presented at National Symphosia on Cellular and Molecular
Biophysics; Jan 14-17,2004 at National institute of Mental Health and Neuro Sciences at Banglore, India.
REFERENCES:
1. Dr. Thomas Einhorn, MD
Professor, Biomedical Engineering
Professor and Chairman, Orthopedic Surgery
720 Harrison avenue, Suite 805 Boston MA 02118
phone: (617) 638-8435
fax: (617) 638-8493
Email: teinhorn@bu.edu
2. Louis C. Gerstenfeld, Ph.D
Associate Professor, Department of Orthopedic Surgery;
Director of Musculoskeletal Research Laboratory
715 Albany St., R-2, Boston MA 02118-2394
617/414-1660
Email: lgersten@bu.edu
3. Darrell N. Kotton, M.D.
The Pulmonary Center, Boston University School of Medicine
715 Albany St., R-304, Boston, MA 02118
Office: 617-638-4860
Email:dkotton@bu.edu
www.kottonlab.com