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Mohammad Mir,

Associate Professor-Virology

College of Veterinary Medicine

E-Mail: mmir@westernu.edu

Phone: 8557

Join year: 2015

Education

Post-Doc (Molecular Virology), 2005, University of New Mexico, Albuquerque, NM, USA

PhD (Structural and Molecular Biology), 2002Biophysics division, Saha Institute of Nuclear Physics, Department of Atomic Energy of India.

Post-Graduate diploma (Biophysics ), 1996, Biophysics division, Saha Institute of Nuclear Physics, Department of Atomic Energy of India.

MS (Biochemistry),1995, University of Kashmir, Srinagar, India

Professional Experience

 

1.Junior Research Fellow: 1996-1997 (Biophysics Division, Saha Institute of Nuclear Physics, Kolkata, India)

2. Senior Research Fellow-I: 198-199 (Biophysics Division, Saha Institute of Nuclear Physics, Kolkata, India)

3. Senior Research Fellow-II: 2000-2002 (Biophysics Division, Saha Institute of Nuclear Physics, Kolkata, India)

4. Post Doctoral Fellow: 2003-2005 (University of New Mexico, Albuquerque, NM, USA)

5. Research Scientist: 2006-2008 (University of New Mexico, Albuquerque, NM, USA)

6. Research Assistant Professor: 2008-2009 (University of New Mexico, Albuquerque, NM, USA)

7. Assistant Professor : 2009-2014 University of Kansas School of Medicine)

8. Associate Professor: 2015-Present (CVM, Western University of Health Sciences)

 

RESEARCH TRAINEES:

I am actively mentoring post docs and graduate students.  The training involves experimental design, data analysis and presentation, literature review, manuscript and grant writing, group discussion and development of inter personnel and communication skills. All the post docs and graduate students who worked in my lab have published their research in good journals. 

Trainee name at Mir lab                                                                                          Present position

1. Absarul Haque (post doc)    Assistant Professor at King Abdul Aziz University, Jeddah, Saudi Arabia

2. Islam Hussein  (post doc)    Scientist at MIT (Boston)

3. Kanchan Senha (post doc) Scientist  at Tata Institute of Fundamental Research, Mumbai, India

4. Nilshad Salim (post doc)    Post doc at Indiana University

5. Abdul Hasseb (Post doc)   ScientistCase Western Reserve University, Cleveland

6. Zekun Wang (post doc)     Post doc at KUMC, Kansas City, Kansas

7. Erdong Cheng (Graduate student)    Post doc, Pittsburg University Medical Center                                                                                                                                                         

8. Safder S Ganaie (Graduate student)    Graduate student at KUMC, Kansas City,  KS                                                                                                                                             

9. Tania S Bunny (Graduate student)    Graduate studentat the University of Florida                                                                                                                                                           

10. Mary Ashley Rimmer (Graduate student)    Graduate student at KUMC, Kansas City,  KS                                                                                                                                            

11. Alex Little (Undergraduate)    MD-PHD student at Texas

12. Albert Kim (Undergraduate)    At KUMC preparing for Medical school

13. Hassan Maaz (Undergraduate)    At KU preparing for Medical school 

14. Jeeva Subbhia (Post doc)    CVM, Western University of Health Sciences, Pomona, CA

Academic Interests

Bio-molecular recognition:  It always fascinated me how  bio-molecules recognize each other in a precise and specific manner to drive a network of molecular reactions in smooth and timely fashion inside the cell.

Host-Pathogen molecular Cross talk:  The molecular cross talk between pathogen and host factors predicts the out come of infectious disease.  The detailed evaluation of cellular networks, identification and characterization of pathogen and host factors will provide key insights for the development of therapeutic approaches for infectious diseases, posing significant threat to human and animal health.

Therapeutic intervention of infectious diseases:  The machineries replicating the genome of infectious pathogen are not full proof. They make mistakes and hence lead to the emergence virulent strains.  The rapid mutations in the genome impact the bio-molecular recognition and result in the eviction of existing anti-infectious agents. However, the molecular biology and medicinal chemistry research approaches focused on the characterization of new drug targets and synthesis of new therapeutic molecules will overcome the threat from emerging infectious pathogens.  

Teaching Experience

Director of Principles of virology course: I taught this course from 2010-2014 at Kansas University Medical center, and took the responsibility as the director of the course in 2012.  

Director of Advanced virology course. I took the responsibility as the director of this course in 2012. 

Director of “Research in progress” or RIP forum:I took the responsibility as the director of this forum since 2010. 

Medical Education:  I taught with great enthusiasm the virology course to MD students at the school of Medicine, KUMC from 2010-2014. 

Courses

1. Principles of virology (2010-2014, Kansas University Medical center)

2. Molecular Genetics (2010-2014, Kansas University Medicalcelter)

3. Infectious Disease (2010-2014, Kansas University Medical Center)

4. Advanced virology (2011-2014, Kansas University Medical center)

5. Problem based learning (2011-2014, Kansas University Medical center)

6. Host-Pathogen interactions (2012-2014, Kansas University Medical center)

7. Problem based learning, PBL (2015-present, CVM, Western University of Health Sciences)

Philosophy

Learning requires a prepared mind.  I believe a powerful tool for an educator is to create motivation among students for the subject material. Clean understanding of basic concepts lays down a strong foundation for acquiring additional knowledge, generating new hypothesis and finding correct solutions in the process of learning. Knowledge gained through problem based learning, independent thinking and analytical reasoning has implicit memory. 

Research Interest

RNA viruses use RNA dependent RNA polymerase (RdRp) to replicate their genome. The emergence of virulent RNA virus strains due to lack of proof reading activity in RdRp has witnessed deadly outbreaks in the human history.The research in Mir laboratory focuses on the replication of negative strand RNA viruses. We are interested to delineate the mechanism of cross talk between host and viral factors, helping the virus to establish infection in the host. The broad aim is understand the molecular networks of viral pathogenesis and identify novel targets for therapeutic intervention of viral disease. We use Sin Nombre hantavirus (SNV) and Andes hantavirus (ANDV) as the model system to answer the above fundamental questions of broad range application and significance. Hantaviruses, the members of the Bunyaviridae family are tri-segmented negative sense RNA viruses whose infection causes hantavirus cardiopulmonary syndrome and hemorrhagic fever with renal syndrome, having mortality rates of 50% and 15%, respectively. Annually 150,000 to 200,000 cases of hantavirus infection are reported worldwide, and there is no vaccine or antiviral therapeutic available for this viral illness. A brief description of current projects focused on both basic and translation research in Mir lab is provided below.

Cap snatching mechanism of transcription initiation: More than three hundred negative strand RNA viruses from the Orthomyxoviridae, Bunyaviridae and Arenaviridae families use cap snatching mechanism for transcription initiation. During this mechanism viral RdRp cleaves the host cell mRNA 10-20 nucleotides downstream of the 5’ cap. The resulting capped RNA fragment is used as primer by RdRp to initiate transcription. Interestingly, host cells contain an elegant decapping system to remove the 5’ caps from host cell mRNAs after the completion of their translation. Decapping of host cell mRNAs is prerequisite for their degradation. Bulk host mRNA degradation takes place in desecrate cytoplasmic foci called P-bodies, raising questions that how are these viruses able to snatch caps from host cell mRNAs in the presence of active cytoplasmic decapping machinery. Our research is focused to determine how hantaviruses evade the host decapping machinery for efficient cap-snatching. We previously reported that hantavirus nucleocapsid protein specifically binds to the host mRNA caps and protects them from the attack of host decapping machinery. The rescued capped mRNA fragments up to 180 nucleotides in length are sequestered in P-bodies by hantavirus nucleocapsid protein. We are interested to know how the sequestered capped mRNA fragments in P-bodies are further processed to generate short RNA primers of appropriate length and specificity.

Translation control of viral mRNA: Despite the tight regulation of eukaryotic translation machinery, viruses have evolved selfish strategies to favor the translation of viral mRNAs in the host cell cytoplasm where cellular transcripts are competing for the same translation apparatus. We have recently found that hantaviruses have evolved a unique translation strategy that lures the host translation machinery for the preferential translation of viral mRNA. We are currently interested to determine if this translation strategy regulates the host gene expression at translational level. We propose that hantaviruses also use this translation strategy to up-regulate the translation of host cell factors required for the establishment of virus infection in the host cell.   

Autophagic degradation of hantavirus glycoprotein:Hantavirus glycoprotein precursor (GPC) is post-  translationally cleaved into two glycoproteins Gn and Gc, which are incorporated into virus envelope in a mature virion. We recently made an interesting observation that Gn is post-translationally degraded by the host autophagy machinery during the early stages of virus replication cycle. Selective degradation of Gn by the host autophagy machinery regulates intrinsic steady state levels of Gn. Inhibition of host autophagy machinery rescued Gn from degradation.  However, the rescued Gn dramatically inhibited virus replication in the host cell. Gn is an important structural component of the virion, it escapes autophagic degradation during the assembly and packaging phase of the virus replication cycle by an unknown mechanism. These observation have raised interesting questions for further study.

Therapeutic intervention of hantavirus disease. From our basic research avenues we have identified the interaction between hantavirus nucloecapsid protein and viral mRNA 5’ untranslated region (UTR) as a novel target for therapeutic intervention of hantavirus disease. We developed a fluorescence based high throughput screening assay to monitor the interaction between N-protein and viral mRNA 5’ UTR. The assay was used to screen a chemical library of 100,000 chemical compounds to identify inhibitors that block this interaction. We have identified a novel lead inhibitor that selectively binds to the N-protein and inhibits N protein-UTR interaction with high potency.  The inhibitor is well tolerated by cells and is under further development as a potential anti-hantaviral therapeutic.  

Research Grant

 

Principal Investigator

Title of Grant/Contract

Funding Source

Direct Costs

Inclusive Years of Award

Mohammad Mir

Role of Hantavirus nucleocapsid protein in viral mRNA “cap snatching”

University of New Mexico

$30,000

2009 -2009

Mohammad Mir

Role of Cellular P-bodies and Hantavirus Nucleocapsid protein in Viral mRNA Cap Snatching

NIH/NIAID R21 AI083672

$275,000

2009-2012

Mohammad Mir

Mechanics of hantaviral nucleocapsid protein mediated translation initiation of viral mRNA

COBRA

NCRR/NIH

RR016443

$425,000

2009-2012

Mohammad Mir

Identification and characterization of inhibitors for hantavirus replication

NIH/NIAID

R01AI095236

$750,000

2011-2014

Mohammad Mir

Characterization of hantavirus N protein-mediated translation mechanism

NIH/NIAID

R21AI097355

$275,000

2012-2014

Mohammad Mir

Regulation of host gene expression by hantavirus nucleocapsid protein mediated

COBRE

5 P30 GM103326-03

$55,000

2014-2014

Mohammad Mir

Cap snatching mechanism of transcription initiation and therapeutic intervention

KINBRE-P20 GM103418

$35,000

2014-2014

Mohammad Mir

X-ray crystallographic studies of hantavirus nucleocapsid protein

COBRE (KU, Lawrence)

$65,000

2014-2014

Mohammad Mir

Bunyaviridae cap snatching at the cross roads of cellular P-bodies

KINBRE

(Bridge funding)

$35,000

2014-2014

Awards

1. Patent application submitted (Docket number K1262.10071US01): A novel chemical Scaffold with broad-spectrum antiviral activity (application submitted) (2015)

2. A travel award from American Society for Virology to attend the International Union of Microbiological Societies (IMUS 2011) meeting at Sapporo Japan (2011)

3. International Patent(PCT/US09/004150) “A viral nucleocapsid protein as a multifunctional translation initiation factor and increased protein and polypeptide production using same” (2010)

4. MGM Staff Award. This award is given once a year by the Department of Molecular Genetics and Microbiology, University of New Mexico. (2007)

5. GATE. Qualified GATE (Graduate Aptitude Test). This test is held in India to rank Indian students on the bases of merit in all disciplines, including physical, chemical, Mathematical and Biological Sciences (2000)

6. Senior Research Fellowship from Department of Atomic Energy, Government of India (1998)

7.Junior Research Fellowshipfrom Department of Atomic Energy, Government of India (1996)

Organizations

1. American Society for virology: (2005-present) Regular member

2. Biophysical Society:  (2005-present) Regular member

3. American Society for Biochemistry and Molecular Biology: (2005-present) Regular member

Committees

I served in the following committees at KUMC

1. Thesis or dissertation committees of the following students

            A. Mary Ashley Rimmer (Mir lab, KUMC)

            B. Li Chen (Baumann lab, Stowrs institute)

            C. Tania S Bunny (Mir Lab, KUMC)

            D. Yong Luo (Qiu lab, KUMC)

            E. Rachel Olsen (Hardwidge lab, KUMC)

            F. Alexander Dowdell (Zuckert lab, KUMC)

            G. Weiran Shen (Qiu lab, KUMC)

            H. Kellyann Jones(Weinman lab, KUMC)

            I. JosiahCox (Weinman lab, KUMC)

            J. Saswati Biswas (Zuckert lab, KUMC)

2. Inter-disciplinary graduate program in biomedical sciences recruitment committee

3. Department of Microbiology graduate affairs committee

4. Instructional Resources Committee (CVM, Western U, 2015-present)

Publication

Complete List of Published Work in MyBibliography:   https://www.ncbi.nlm.nih.gov/sites/myncbi/14aucy489mrAf/bibliography/51123755/public/?sort=date&direction=ascending.

Mir, MAand Dasgupta, D. Association of the anticancer antibiotic chromomycin A3 with the nucleosome: Role of core histone tail domains in binding process. Biochemistry (2001), 40, 11578-11585

Mir, MAand Dasgupta, D. Interaction of antitumor drug, mithramycin with chromatin. Biochemical and Biophysical Research Communication. (2001), 280, 68-74

Mir, MAand Dasgupta, D. Interaction of mithramycin with chromatin. Indian Journal of Biochemistry and Biophysics, (2001), 38, 71-74

Chaktabarty, S,  Mir, MA and Dasgupta, D. Differential interaction of antitumor antibiotics chromomycin A3 and mithramycin with d(TATGCATA)2 in presence of Mg2+. Biopolymers , (2001), 62, 131-140

Mir, MAand Dasgupta, D. Association of anticancer drug mithramycin with H1 depletedchromatin: a    comparison with native chromatin. Journal of Inorganic Biochemistry, (2003), 94, 72-77.

 Mir, MA, Majee, S., Das, S. and Dasgupta, D. Association of chromatin with anticancer antibiotics mithramycin and chromomycin A3. Bioor Med. Chemistry, (2003), 11(13)2791-801

Mir, MA,Das, S and Dasgupta, D. N -terminal tail domains of core histones in nucleosome block access of anticancer drugs, mithramycin and chromomycin, to the nucleosomal DNA. Biophysical Chemistry, (2004) ,109:121-135

Mir, MAand A. T Panganiban. Trimeric hantavirus nucleocapsid protein binds specifically with the viral RNA panhandle. J. Virol. (2004) Aug;78(15):8281-8

Mir, MAand A. T Panganiban. The hantavirus nucleocapsid protein recognizes specific features of the viral RNA panhandle and is altered in conformation upon binding. J Virol. (2005) Feb;79(3):1824¬35.

Mir, MAand A. T Panganiban. Characterization of RNA chaperon activity of Hantavirus Nucleocapsid protein activity. J. Virol, (2006) Jul;80 13:6276-85.

Mir, MA, B. Brown, B.L. Hjelle, W.A Duran and A. T Panganiban . Hantavirus N protein exhibits genus specific recognition of the v RNA panhandle, (2006), J. Virol. 13:6276-850

Mir, MAand A. T Panganiban. Hantavirus Nucleocapsid protein is an RNA Chaperon. RNA, (2006), 12:272-282.

Mir, MA, and A. T Panganiban: A protein that replaces entire eIF4F complex, EMBO Journal, (2008), Dec 3;27(23):3129-39

Mir. MA, Hjelle, B. Ye, C and A. T Panganiban: Cap snatching Revised: Viral storage of cellular 5’mRNA caps in P bodies: Proc. Natl. Acad. Sci. USA, 2008, 2008 Dec 9;105(49):19294-9.T Panganiban and

Mir, MA: Bunyavirus N: elF4F surrogate and Cap –Guardian: Cell Cycle, 2009, May 1; 8(9): 1332-7.

Mir, MA*and A. T Panganiban: The triplet repeats of the Sin Nombre hantavirus 5' untranslated region are sufficient in cis for nucleocapsid-mediated translation initiation: J. Virology, (2010) Sep;84(17):8937-44.

Mir, MA*, Hantaviruses, Clinics in Laboratory Medicine, published by Elsevier. 2010 Mar; 30(1):67-91.

Mir, MA*, Sheema S, Abdul A, Haque A: Hantavirus nucleocapsid protein has distinct m7G cap and RNA binding sites, J. Biol. Chem.  (2010) Apr 9;285(15):11357-68. Epub 2010 Feb 17

Haque, A and Mir, MA* : Interaction of hantavirus nucleocapsid protein with ribosomal protein S19 (RPS19). J virology, (2010). Dec;84(23):12450-3. Epub 2010 Sep 15

Cheng, E. Haque, A. Rimmer, MA. Hussein, I. Sheema, S. Little, A and Mir, MA*: Characterization of the interaction between hantavirus nucleocapsid protein (N) and ribosomal protein S19 (RPS19): J. Biol. Chem, (2011).Apr 1;286(13):11814-24. Epub 2011 Feb 4.

Islam T. M. Hussein, Hasseb, A. Haque, A. &  Mir, MA*:  Recent advances in hantavirus molecular biology and disease: Advances in Applied Microbiology, 2011, 74:35-75

Islam T. M. Hussein, Erdong Cheng, Michael J. Werle, Sheema Sheema and  Mir MA*: Autophagic clearance of Sin Nombre hantavirus glycoprotein Gn promotes virus replication in cells, J. Virology, (2012), Jul;86(14):7520-9. doi: 10.1128/JVI.07204-11. Epub 2012 May 2

Cheng E, Mir MA*. Signatures of host mRNA 5' terminus for efficient hantavirus cap snatching.J Virol, (2012) Sep;86(18):10173-85. doi: 10.1128/JVI.05560-11. Epub 2012 Jul 11.

Islam T. M. Hussein, Mir, MA*How hantaviruses modulate the basic cellular pathways during infection. Front Biosci (Elite Ed). 2013 Jan 1;5:154-66.

Ganaie, S.S and Mir MA *. The role of viral genomic RNA and nucleocapsid protein in the autophagic clearance of hantavirus glycoprotein Gn. Virus Res.2014 Jan 8. pii: S0168-1702(13)00480-2.

Cheng E and Mir, MA*. Crimean Congo Hemorrhagic fever virus nucleocapsid protein favorus mRNA translation with the assistance of viral mRNA 5’ UTR. J. Virology (Under review)

Safdar S Ganaie , Absarul Haque, Erdong Cheng, Tania S. Bonny, Nilsahd N. Salim and Mir MA*. RPS19 binding domain provides key insights into hantavirus N-mediated translation initiation mechanism. Biochemical Journal. 2014 Jul 25. [Epub ahead of print]

Cheng E and Mir MA*.The interaction between hantavirus nucleocapsid protein and viral RdRp is required for viral mRNA synthesis J Virol. 2014 Aug 1;88(15):8706-8712. Epub 2014 May 21.

Wang Z and Mir MA*. Andes virus nucleocapsid protein interrupts PKR dimerization to counteract the host interference in viral protein synthesis. J. Virol. 2015 Nov 19. pii: JVI.02347-14. [Epub ahead of print]

Salim N, Ganaie S.S, Roy, A, Jeeva Subbiah and Mir MA*. Targeting a novel RNA-protein interaction for therapeutic intervention of hantavirus disease. J. Biol, Chem. 2016.   Oct 12. pii: jbc.M116.750729

Narrative

I am a multidisciplinary virologist interested in molecular mechanism of virus replication and therapeutic intervention of viral diseases.  I am enthusiastic to train next generation of virologists with a background in veterinary sciences at the College of veterinary medicine, Western University of Health Sciences.  The veterinarians with research experiences in cutting edge virology will serve as specialized lead work force in the frontier areas of infectious disease.