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Matthew B. Frieman, PhD

Academic Title:

Associate Professor

Primary Appointment:

Microbiology and Immunology

Location:

BRB, 3-020

Phone (Primary):

410-706-2539

Education and Training

  • Washington University in St Louis, BA, Biology, 1994-1998
  • Johns Hopkins University School of Medicine, Baltimore MD, Cellular and Molecular Medicine Graduate Program, Department of Molecular Biology and Genetics, PhD, 1998-2004
  • University of North Carolina at Chapel Hill, Post-doctoral fellow in the lab of Dr. Ralph Baric, Department of Epidemiology/Department of Microbiology and Immunology, 2004-2009

 

Biosketch

I have an interest in the understanding of cell biology as it pertains to pathogenesis. My background began in the mechanism of “nucleolar dominance” in Brassica species while an undergraduate in the laboratory of Dr. Craig Pikaard (Washington University in St. Louis). My graduate work in the laboratory of Dr. Brendan Cormack at The Johns Hopkins University focused on yeast genetics and cell wall adhesins of Candida glabrata using S. cerevisiae as a model where I greatly expanded my genetics, molecular biology and cell biology background. I then moved to the laboratory of Dr. Ralph Baric at the University of North Carolina where my molecular and cell biology background were extended to understanding SARS-CoV replication, innate immune antagonism and pathogenesis. I currently am an Associate Professor at the University of Maryland School of Medicine focusing on the host response to SARS-CoV and MERS-CoV. At The University of Maryland School of Medicine I have mentored 4 undergraduate students, 3 graduate students (2 graduated), 2 post-doctoral fellows and teach both graduate students and medical students lectures on virology and infectious diseases.

Our focus of the lab is on the interaction between SARS-CoV, MERS-CoV and the host cell/organism. We use the Severe acute Respiratory Virus (SARS-CoV) and the Middle East Respiratory Syndrome (MERS-CoV) as our model systems to identify how viral proteins alter the host response and how the host responds to the viral infection. This understanding aids in the identification of proteins and pathways that are critical for viral pathogenesis and therefore targets for therapeutics. 

Research/Clinical Keywords

Coronavirus, MERS, SARS, Pathogenesis, anti-viral, therapeutics, diabetes, DPP4, lung, Zika virus

Highlighted Publications

Coleman CM, Sisk JM, Halasz G, Zhong J, Beck SE, Matthews KL, Venkataraman T, Rajagopalan S, Kyratsous CA, Frieman MB. CD8+ T cells and Macrophages Regulate Pathogenesis in a Mouse Model of MERS-CoV Disease. J Virol. 2016 Oct26. pii:JVI.01825-16.

Coleman CM, Sisk JM, Mingo RM, Nelson EA, White JM, Frieman MB. Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion. J Virol. 2016 Sep 12;90(19):8924-33. doi: 10.1128/JVI.01429-16. 

Pascal KE, Coleman CM, Mujica AO, Kamat V, Badithe A, Fairhurst J, Hunt C, Strein J, Berrebi A, Sisk JM, Matthews KL, Babb R, Chen G, Lai KM, Huang TT, Olson W, Yancopoulos GD, Stahl N, Frieman MB, Kyratsous CA.  Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection.  Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):8738-43.

Luke T, Wu H, Zhao J, Channappanavar R, Coleman CM, Jiao JA, Matsushita H, Liu Y, Postnikova EN, Ork BL, Glenn G, Flyer D, Defang G, Raviprakash K, Kochel T, Wang J, Nie W, Smith G, Hensley LE, Olinger GG, Kuhn JH, Holbrook MR, Johnson RF,Perlman S, Sullivan E, Frieman MB. Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo. Sci Transl Med. 2016 Feb17;8(326):326ra21. doi: 10.1126/scitranslmed.aaf1061. PubMed PMID: 26888429.

Taylor JK, Coleman CM, Postel S, Sisk JM, Bernbaum JG, Venkataraman T, Sundberg EJ, Frieman MB. Severe Acute Respiratory Syndrome Coronavirus ORF7a Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel Mechanism of Glycosylation Interference. J Virol. 2015 Dec;89(23):11820-33. doi:10.1128/JVI.02274-15. PubMed PMID: 26378163; PubMed Central PMCID: PMC4645327.

Dyall, J., C. M. Coleman, B. J. Hart, T. Venkataraman, M. R. Holbrook, J. Kindrachuk, R. F. Johnson, G. G. Olinger, Jr., P. B. Jahrling, M. Laidlaw, Hensley L, and Frieman M. 2014. Repurposing of clinically developed drugs for treatment of middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother 58:4885-93. PubMed PMID: 24841273.

Page, C., L. Goicochea, K. Matthews, Y. Zhang, P. Klover, M. J. Holtzman, L. Hennighausen, and M. Frieman. 2012. Induction of alternatively activated macrophages enhances pathogenesis during severe acute respiratory syndrome coronavirus infection. J Virol 86:13334-49. PubMed PMID: 23015710; PubMed Central PMCID: PMC3503056.

Additional Publication Citations

1: Moser LA, Ramirez-Carvajal L, Puri V, Pauszek SJ, Matthews K, Dilley KA,

Mullan C, McGraw J, Khayat M, Beeri K, Yee A, Dugan V, Heise MT, Frieman MB,

Rodriguez LL, Bernard KA, Wentworth DE, Stockwell TB, Shabman RS. A Universal

Next-Generation Sequencing Protocol To Generate Noninfectious Barcoded cDNA

Libraries from High-Containment RNA Viruses. mSystems. 2016 Jun 7;1(3). pii:

e00039-15. PubMed PMID: 27822536; PubMed Central PMCID: PMC5069770.

 

 

2: Wirblich C, Coleman CM, Kurup D, Abraham TS, Bernbaum JG, Jahrling PB, Hensley

LE, Johnson RF, Frieman MB, Schnell MJ. One-Health: A Safe, Efficient Dual-use

Vaccine for Humans and Animals against MERS-CoV and Rabies Virus. J Virol. 2016

Nov 2. pii: JVI.02040-16. [Epub ahead of print] PubMed PMID: 27807241.

 

 

3: Coleman CM, Sisk JM, Halasz G, Zhong J, Beck SE, Matthews KL, Venkataraman T,

Rajagopalan S, Kyratsous CA, Frieman MB. CD8+ T cells and Macrophages Regulate

Pathogenesis in a Mouse Model of MERS-CoV Disease. J Virol. 2016 Oct 26. pii:

JVI.01825-16. [Epub ahead of print] PubMed PMID: 27795435.

 

 

4: Sisk JM, Frieman MB. Screening of FDA-Approved Drugs for Treatment of Emerging

Pathogens. ACS Infect Dis. 2015 Sep 11;1(9):401-2. doi:

10.1021/acsinfecdis.5b00089. PubMed PMID: 27617922.

 

 

5: Coleman CM, Sisk JM, Mingo RM, Nelson EA, White JM, Frieman MB. Abelson Kinase

Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus

and Middle East Respiratory Syndrome Coronavirus Fusion. J Virol. 2016 Sep

12;90(19):8924-33. doi: 10.1128/JVI.01429-16. PubMed PMID: 27466418; PubMed

Central PMCID: PMC5021412.

 

 

6: Luke T, Wu H, Zhao J, Channappanavar R, Coleman CM, Jiao JA, Matsushita H, Liu

Y, Postnikova EN, Ork BL, Glenn G, Flyer D, Defang G, Raviprakash K, Kochel T,

Wang J, Nie W, Smith G, Hensley LE, Olinger GG, Kuhn JH, Holbrook MR, Johnson RF,

Perlman S, Sullivan E, Frieman MB. Human polyclonal immunoglobulin G from

transchromosomic bovines inhibits MERS-CoV in vivo. Sci Transl Med. 2016 Feb

17;8(326):326ra21. doi: 10.1126/scitranslmed.aaf1061. PubMed PMID: 26888429.

 

 

7: Gralinski LE, Ferris MT, Aylor DL, Whitmore AC, Green R, Frieman MB, Deming D,

Menachery VD, Miller DR, Buus RJ, Bell TA, Churchill GA, Threadgill DW, Katze MG,

McMillan L, Valdar W, Heise MT, Pardo-Manuel de Villena F, Baric RS. Genome Wide

Identification of SARS-CoV Susceptibility Loci Using the Collaborative Cross.

PLoS Genet. 2015 Oct 9;11(10):e1005504. doi: 10.1371/journal.pgen.1005504. PubMed

PMID: 26452100; PubMed Central PMCID: PMC4599853.

 

 

8: Taylor JK, Coleman CM, Postel S, Sisk JM, Bernbaum JG, Venkataraman T,

Sundberg EJ, Frieman MB. Severe Acute Respiratory Syndrome Coronavirus ORF7a

Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel Mechanism

of Glycosylation Interference. J Virol. 2015 Dec;89(23):11820-33. doi:

10.1128/JVI.02274-15. PubMed PMID: 26378163; PubMed Central PMCID: PMC4645327.

 

 

9: Coleman CM, Frieman MB. Growth and Quantification of MERS-CoV Infection. Curr

Protoc Microbiol. 2015 May 1;37:15E.2.1-9. doi: 10.1002/9780471729259.mc15e02s37.

PubMed PMID: 26344219; PubMed Central PMCID: PMC4735735.

 

 

10: Pascal KE, Coleman CM, Mujica AO, Kamat V, Badithe A, Fairhurst J, Hunt C,

Strein J, Berrebi A, Sisk JM, Matthews KL, Babb R, Chen G, Lai KM, Huang TT,

Olson W, Yancopoulos GD, Stahl N, Frieman MB, Kyratsous CA. Pre- and postexposure

efficacy of fully human antibodies against Spike protein in a novel humanized

mouse model of MERS-CoV infection. Proc Natl Acad Sci U S A. 2015 Jul

14;112(28):8738-43. doi: 10.1073/pnas.1510830112. PubMed PMID: 26124093; PubMed

Central PMCID: PMC4507189.

 

 

11: McSweegan E, Weaver SC, Lecuit M, Frieman M, Morrison TE, Hrynkow S. The

Global Virus Network: Challenging chikungunya. Antiviral Res. 2015

Aug;120:147-52. doi: 10.1016/j.antiviral.2015.06.003. Review. PubMed PMID:

26071007; PubMed Central PMCID: PMC4843800.

 

 

12: Frieman M, Sola I, Enjuanes L. Virus Research. Foreword. Nidoviruses II.

Virus Res. 2015 Apr 16;202:1-2. doi: 10.1016/j.virusres.2015.05.013. PubMed PMID:

26025418.

 

 

13: Mojica SA, Hovis KM, Frieman MB, Tran B, Hsia RC, Ravel J, Jenkins-Houk C,

Wilson KL, Bavoil PM. SINC, a type III secreted protein of Chlamydia psittaci,

targets the inner nuclear membrane of infected cells and uninfected neighbors.

Mol Biol Cell. 2015 May 15;26(10):1918-34. doi: 10.1091/mbc.E14-11-1530. PubMed

PMID: 25788290; PubMed Central PMCID: PMC4436835.

 

 

14: Astry B, Venkatesha SH, Laurence A, Christensen-Quick A, Garzino-Demo A,

Frieman MB, O'Shea JJ, Moudgil KD. Celastrol, a Chinese herbal compound, controls

autoimmune inflammation by altering the balance of pathogenic and regulatory T

cells in the target organ. Clin Immunol. 2015 Apr;157(2):228-38. doi:

10.1016/j.clim.2015.01.011. PubMed PMID: 25660987; PubMed Central PMCID:

PMC4410084.

 

 

15: Nita-Lazar M, Banerjee A, Feng C, Amin MN, Frieman MB, Chen WH, Cross AS,

Wang LX, Vasta GR. Desialylation of airway epithelial cells during influenza

virus infection enhances pneumococcal adhesion via galectin binding. Mol Immunol.

2015 May;65(1):1-16. doi: 10.1016/j.molimm.2014.12.010. PubMed PMID: 25597246;

PubMed Central PMCID: PMC4344939.

 

 

16: Kindrachuk J, Ork B, Hart BJ, Mazur S, Holbrook MR, Frieman MB, Traynor D,

Johnson RF, Dyall J, Kuhn JH, Olinger GG, Hensley LE, Jahrling PB. Antiviral

potential of ERK/MAPK and PI3K/AKT/mTOR signaling modulation for Middle East

respiratory syndrome coronavirus infection as identified by temporal kinome

analysis. Antimicrob Agents Chemother. 2015 Feb;59(2):1088-99. doi:

10.1128/AAC.03659-14. PubMed PMID: 25487801; PubMed Central PMCID: PMC4335870.

 

 

17: Enjuanes L, Sola I, Frieman MB. Virus Research. Nidoviruses I. Foreword.

Virus Res. 2014 Dec 19;194:1-2. doi: 10.1016/j.virusres.2014.11.017. PubMed PMID:

25483881.

 

 

18: Matthews K, Schäfer A, Pham A, Frieman M. The SARS coronavirus papain like

protease can inhibit IRF3 at a post activation step that requires

deubiquitination activity. Virol J. 2014 Dec 7;11:209. doi:

10.1186/s12985-014-0209-9. PubMed PMID: 25481026; PubMed Central PMCID:

PMC4272517.

 

 

19: Coleman CM, Frieman MB. Treating MERS-CoV during an outbreak. Lancet Infect

Dis. 2014 Nov;14(11):1030-1. doi: 10.1016/S1473-3099(14)70939-9. PubMed PMID:

25278219.

 

 

20: Li J, Sun W, Subrahmanyam PB, Page C, Younger KM, Tiper IV, Frieman M,

Kimball AS, Webb TJ. NKT Cell Responses to B Cell Lymphoma. Med Sci (Basel). 2014

Jun 1;2(2):82-97. PubMed PMID: 24955247; PubMed Central PMCID: PMC4063678.

 

 

21: Ladner JT, Beitzel B, Chain PS, Davenport MG, Donaldson EF, Frieman M,

Kugelman JR, Kuhn JH, O'Rear J, Sabeti PC, Wentworth DE, Wiley MR, Yu GY; Threat

Characterization Consortium., Sozhamannan S, Bradburne C, Palacios G. Standards

for sequencing viral genomes in the era of high-throughput sequencing. MBio. 2014

Jun 17;5(3):e01360-14. doi: 10.1128/mBio.01360-14. PubMed PMID: 24939889; PubMed

Central PMCID: PMC4068259.

 

 

22: Frieman M. The art of war: battles between virus and host. Curr Opin Virol.

2014 Jun;6:76-7. doi: 10.1016/j.coviro.2014.05.001. PubMed PMID: 24886699; PubMed

Central PMCID: PMC4422063.

 

 

23: Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J,

Johnson RF, Olinger GG Jr, Jahrling PB, Laidlaw M, Johansen LM, Lear-Rooney CM,

Glass PJ, Hensley LE, Frieman MB. Repurposing of clinically developed drugs for

treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob

Agents Chemother. 2014 Aug;58(8):4885-93. doi: 10.1128/AAC.03036-14. PubMed PMID:

24841273; PubMed Central PMCID: PMC4136000.

 

 

24: Adedeji AO, Singh K, Kassim A, Coleman CM, Elliott R, Weiss SR, Frieman MB,

Sarafianos SG. Evaluation of SSYA10-001 as a replication inhibitor of severe

acute respiratory syndrome, mouse hepatitis, and Middle East respiratory syndrome

coronaviruses. Antimicrob Agents Chemother. 2014 Aug;58(8):4894-8. doi:

10.1128/AAC.02994-14. PubMed PMID: 24841268; PubMed Central PMCID: PMC4136041.

 

 

25: Coleman CM, Liu YV, Mu H, Taylor JK, Massare M, Flyer DC, Glenn GM, Smith GE,

Frieman MB. Purified coronavirus spike protein nanoparticles induce coronavirus

neutralizing antibodies in mice. Vaccine. 2014 May 30;32(26):3169-74. doi:

10.1016/j.vaccine.2014.04.016. PubMed PMID: 24736006; PubMed Central PMCID:

PMC4058772.

 

 

26: Coleman CM, Frieman MB. Coronaviruses: important emerging human pathogens. J

Virol. 2014 May;88(10):5209-12. doi: 10.1128/JVI.03488-13. Review. PubMed PMID:

24600003; PubMed Central PMCID: PMC4019136.

 

 

27: Matthews KL, Coleman CM, van der Meer Y, Snijder EJ, Frieman MB. The

ORF4b-encoded accessory proteins of Middle East respiratory syndrome coronavirus

and two related bat coronaviruses localize to the nucleus and inhibit innate

immune signalling. J Gen Virol. 2014 Apr;95(Pt 4):874-82. doi:

10.1099/vir.0.062059-0. PubMed PMID: 24443473; PubMed Central PMCID: PMC3973478.

 

 

28: Kim WK, Jain D, Sánchez MD, Koziol-White CJ, Matthews K, Ge MQ, Haczku A,

Panettieri RA Jr, Frieman MB, López CB. Deficiency of melanoma

differentiation-associated protein 5 results in exacerbated chronic postviral

lung inflammation. Am J Respir Crit Care Med. 2014 Feb 15;189(4):437-48. doi:

10.1164/rccm.201307-1338OC. PubMed PMID: 24417465; PubMed Central PMCID:

PMC3977719.

 

 

29: Hart BJ, Dyall J, Postnikova E, Zhou H, Kindrachuk J, Johnson RF, Olinger GG

Jr, Frieman MB, Holbrook MR, Jahrling PB, Hensley L. Interferon-β and

mycophenolic acid are potent inhibitors of Middle East respiratory syndrome

coronavirus in cell-based assays. J Gen Virol. 2014 Mar;95(Pt 3):571-7. doi:

10.1099/vir.0.061911-0. PubMed PMID: 24323636; PubMed Central PMCID: PMC3929173.

 

 

30: Coleman CM, Matthews KL, Goicochea L, Frieman MB. Wild-type and innate

immune-deficient mice are not susceptible to the Middle East respiratory syndrome

coronavirus. J Gen Virol. 2014 Feb;95(Pt 2):408-12. doi: 10.1099/vir.0.060640-0.

PubMed PMID: 24197535; PubMed Central PMCID: PMC3917065.

 

 

31: Coleman CM, Frieman MB. Emergence of the Middle East respiratory syndrome

coronavirus. PLoS Pathog. 2013;9(9):e1003595. doi: 10.1371/journal.ppat.1003595.

Review. PubMed PMID: 24039577; PubMed Central PMCID: PMC3764217.

 

 

32: Page C, Goicochea L, Matthews K, Zhang Y, Klover P, Holtzman MJ, Hennighausen

L, Frieman M. Induction of alternatively activated macrophages enhances

pathogenesis during severe acute respiratory syndrome coronavirus infection. J

Virol. 2012 Dec;86(24):13334-49. doi: 10.1128/JVI.01689-12. PubMed PMID:

23015710; PubMed Central PMCID: PMC3503056.

 

 

33: Huynh J, Li S, Yount B, Smith A, Sturges L, Olsen JC, Nagel J, Johnson JB,

Agnihothram S, Gates JE, Frieman MB, Baric RS, Donaldson EF. Evidence supporting

a zoonotic origin of human coronavirus strain NL63. J Virol. 2012

Dec;86(23):12816-25. doi: 10.1128/JVI.00906-12. PubMed PMID: 22993147; PubMed

Central PMCID: PMC3497669.

 

 

34: Frieman M, Basu D, Matthews K, Taylor J, Jones G, Pickles R, Baric R, Engel

DA. Yeast based small molecule screen for inhibitors of SARS-CoV. PLoS One.

2011;6(12):e28479. doi: 10.1371/journal.pone.0028479. PubMed PMID: 22164298;

PubMed Central PMCID: PMC3229576.

 

 

35: Peng X, Gralinski L, Ferris MT, Frieman MB, Thomas MJ, Proll S, Korth MJ,

Tisoncik JR, Heise M, Luo S, Schroth GP, Tumpey TM, Li C, Kawaoka Y, Baric RS,

Katze MG. Integrative deep sequencing of the mouse lung transcriptome reveals

differential expression of diverse classes of small RNAs in response to

respiratory virus infection. MBio. 2011 Nov 15;2(6). pii: e00198-11. doi:

10.1128/mBio.00198-11. PubMed PMID: 22086488; PubMed Central PMCID: PMC3221602.

 

 

36: Frieman M, Yount B, Agnihothram S, Page C, Donaldson E, Roberts A, Vogel L,

Woodruff B, Scorpio D, Subbarao K, Baric RS. Molecular determinants of severe

acute respiratory syndrome coronavirus pathogenesis and virulence in young and

aged mouse models of human disease. J Virol. 2012 Jan;86(2):884-97. doi:

10.1128/JVI.05957-11. PubMed PMID: 22072787; PubMed Central PMCID: PMC3255850.

 

 

37: Chen WH, Toapanta FR, Shirey KA, Zhang L, Giannelou A, Page C, Frieman MB,

Vogel SN, Cross AS. Potential role for alternatively activated macrophages in the

secondary bacterial infection during recovery from influenza. Immunol Lett. 2012

Jan 30;141(2):227-34. doi: 10.1016/j.imlet.2011.10.009. PubMed PMID: 22037624;

PubMed Central PMCID: PMC3243824.

 

 

38: Aylor DL, Valdar W, Foulds-Mathes W, Buus RJ, Verdugo RA, Baric RS, Ferris

MT, Frelinger JA, Heise M, Frieman MB, Gralinski LE, Bell TA, Didion JD, Hua K,

Nehrenberg DL, Powell CL, Steigerwalt J, Xie Y, Kelada SN, Collins FS, Yang IV,

Schwartz DA, Branstetter LA, Chesler EJ, Miller DR, Spence J, Liu EY, McMillan L,

Sarkar A, Wang J, Wang W, Zhang Q, Broman KW, Korstanje R, Durrant C, Mott R,

Iraqi FA, Pomp D, Threadgill D, de Villena FP, Churchill GA. Genetic analysis of

complex traits in the emerging Collaborative Cross. Genome Res. 2011

Aug;21(8):1213-22. doi: 10.1101/gr.111310.110. PubMed PMID: 21406540; PubMed

Central PMCID: PMC3149489.

 

 

39: Peng X, Gralinski L, Armour CD, Ferris MT, Thomas MJ, Proll S,

Bradel-Tretheway BG, Korth MJ, Castle JC, Biery MC, Bouzek HK, Haynor DR, Frieman

MB, Heise M, Raymond CK, Baric RS, Katze MG. Unique signatures of long noncoding

RNA expression in response to virus infection and altered innate immune

signaling. MBio. 2010 Oct 26;1(5). pii: e00206-10. doi: 10.1128/mBio.00206-10.

PubMed PMID: 20978541; PubMed Central PMCID: PMC2962437.

 

 

40: Donaldson EF, Haskew AN, Gates JE, Huynh J, Moore CJ, Frieman MB. Metagenomic

analysis of the viromes of three North American bat species: viral diversity

among different bat species that share a common habitat. J Virol. 2010

Dec;84(24):13004-18. doi: 10.1128/JVI.01255-10. PubMed PMID: 20926577; PubMed

Central PMCID: PMC3004358.

 

 

41: Zornetzer GA, Frieman MB, Rosenzweig E, Korth MJ, Page C, Baric RS, Katze MG.

Transcriptomic analysis reveals a mechanism for a prefibrotic phenotype in STAT1

knockout mice during severe acute respiratory syndrome coronavirus infection. J

Virol. 2010 Nov;84(21):11297-309. doi: 10.1128/JVI.01130-10. PubMed PMID:

20702617; PubMed Central PMCID: PMC2953159.

 

 

42: Frieman MB, Chen J, Morrison TE, Whitmore A, Funkhouser W, Ward JM, Lamirande

EW, Roberts A, Heise M, Subbarao K, Baric RS. SARS-CoV pathogenesis is regulated

by a STAT1 dependent but a type I, II and III interferon receptor independent

mechanism. PLoS Pathog. 2010 Apr 8;6(4):e1000849. doi:

10.1371/journal.ppat.1000849. PubMed PMID: 20386712; PubMed Central PMCID:

PMC2851658.

 

 

43: Rockx B, Donaldson E, Frieman M, Sheahan T, Corti D, Lanzavecchia A, Baric

RS. Escape from human monoclonal antibody neutralization affects in vitro and in

vivo fitness of severe acute respiratory syndrome coronavirus. J Infect Dis. 2010

Mar 15;201(6):946-55. doi: 10.1086/651022. PubMed PMID: 20144042; PubMed Central

PMCID: PMC2826557.

 

 

44: Freundt EC, Yu L, Goldsmith CS, Welsh S, Cheng A, Yount B, Liu W, Frieman MB,

Buchholz UJ, Screaton GR, Lippincott-Schwartz J, Zaki SR, Xu XN, Baric RS,

Subbarao K, Lenardo MJ. The open reading frame 3a protein of severe acute

respiratory syndrome-associated coronavirus promotes membrane rearrangement and

cell death. J Virol. 2010 Jan;84(2):1097-109. doi: 10.1128/JVI.01662-09. PubMed

PMID: 19889773; PubMed Central PMCID: PMC2798367.

 

 

45: Day CW, Baric R, Cai SX, Frieman M, Kumaki Y, Morrey JD, Smee DF, Barnard DL.

A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral

agents in vitro and in vivo. Virology. 2009 Dec 20;395(2):210-22. doi:

10.1016/j.virol.2009.09.023. PubMed PMID: 19853271; PubMed Central PMCID:

PMC2787736.

 

 

46: Rockx B, Baas T, Zornetzer GA, Haagmans B, Sheahan T, Frieman M, Dyer MD,

Teal TH, Proll S, van den Brand J, Baric R, Katze MG. Early upregulation of acute

respiratory distress syndrome-associated cytokines promotes lethal disease in an

aged-mouse model of severe acute respiratory syndrome coronavirus infection. J

Virol. 2009 Jul;83(14):7062-74. doi: 10.1128/JVI.00127-09. Erratum in: J Virol.

2009 Sep;83(17):9022. PubMed PMID: 19420084; PubMed Central PMCID: PMC2704758.

 

 

47: Frieman M, Ratia K, Johnston RE, Mesecar AD, Baric RS. Severe acute

respiratory syndrome coronavirus papain-like protease ubiquitin-like domain and

catalytic domain regulate antagonism of IRF3 and NF-kappaB signaling. J Virol.

2009 Jul;83(13):6689-705. doi: 10.1128/JVI.02220-08. PubMed PMID: 19369340;

PubMed Central PMCID: PMC2698564.

 

 

48: Frieman M, Baric R. Mechanisms of severe acute respiratory syndrome

pathogenesis and innate immunomodulation. Microbiol Mol Biol Rev. 2008

Dec;72(4):672-85, Table of Contents. doi: 10.1128/MMBR.00015-08. Review. PubMed

PMID: 19052324; PubMed Central PMCID: PMC2593566.

 

 

49: Basu D, Walkiewicz MP, Frieman M, Baric RS, Auble DT, Engel DA. Novel

influenza virus NS1 antagonists block replication and restore innate immune

function. J Virol. 2009 Feb;83(4):1881-91. doi: 10.1128/JVI.01805-08. PubMed

PMID: 19052087; PubMed Central PMCID: PMC2643796.

 

 

50: Zupancic ML, Frieman M, Smith D, Alvarez RA, Cummings RD, Cormack BP. Glycan

microarray analysis of Candida glabrata adhesin ligand specificity. Mol

Microbiol. 2008 May;68(3):547-59. doi: 10.1111/j.1365-2958.2008.06184.x. PubMed

PMID: 18394144.

 

 

51: Wathelet MG, Orr M, Frieman MB, Baric RS. Severe acute respiratory syndrome

coronavirus evades antiviral signaling: role of nsp1 and rational design of an

attenuated strain. J Virol. 2007 Nov;81(21):11620-33. PubMed PMID: 17715225;

PubMed Central PMCID: PMC2168762.

 

 

52: Frieman M, Yount B, Heise M, Kopecky-Bromberg SA, Palese P, Baric RS. Severe

acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by

sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi

membrane. J Virol. 2007 Sep;81(18):9812-24. PubMed PMID: 17596301; PubMed Central

PMCID: PMC2045396.

 

 

53: Frieman M, Heise M, Baric R. SARS coronavirus and innate immunity. Virus Res.

2008 Apr;133(1):101-12. Review. PubMed PMID: 17451827; PubMed Central PMCID:

PMC2292640.

 

 

54: Kopecky-Bromberg SA, Martínez-Sobrido L, Frieman M, Baric RA, Palese P.

Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6,

and nucleocapsid proteins function as interferon antagonists. J Virol. 2007

Jan;81(2):548-57. PubMed PMID: 17108024; PubMed Central PMCID: PMC1797484.

 

 

55: Baric RS, Sheahan T, Deming D, Donaldson E, Yount B, Sims AC, Roberts RS,

Frieman M, Rockx B. SARS coronavirus vaccine development. Adv Exp Med Biol.

2006;581:553-60. PubMed PMID: 17037597.

 

 

56: Frieman MB, Yount B, Sims AC, Deming DJ, Morrison TE, Sparks J, Denison M,

Heise M, Baric RS. SARS coronavirus accessory ORFs encode luxury functions. Adv

Exp Med Biol. 2006;581:149-52. PubMed PMID: 17037522.

 

 

57: Yount B, Roberts RS, Sims AC, Deming D, Frieman MB, Sparks J, Denison MR,

Davis N, Baric RS. Severe acute respiratory syndrome coronavirus group-specific

open reading frames encode nonessential functions for replication in cell

cultures and mice. J Virol. 2005 Dec;79(23):14909-22. PubMed PMID: 16282490;

PubMed Central PMCID: PMC1287583.

 

 

58: Frieman MB, Cormack BP. Multiple sequence signals determine the distribution

of glycosylphosphatidylinositol proteins between the plasma membrane and cell

wall in Saccharomyces cerevisiae. Microbiology. 2004 Oct;150(Pt 10):3105-14.

PubMed PMID: 15470092.

 

 

59: Frieman MB, Cormack BP. The omega-site sequence of

glycosylphosphatidylinositol-anchored proteins in Saccharomyces cerevisiae can

determine distribution between the membrane and the cell wall. Mol Microbiol.

2003 Nov;50(3):883-96. PubMed PMID: 14617149.

 

 

60: Frieman MB, McCaffery JM, Cormack BP. Modular domain structure in the Candida

glabrata adhesin Epa1p, a beta1,6 glucan-cross-linked cell wall protein. Mol

Microbiol. 2002 Oct;46(2):479-92. PubMed PMID: 12406223.

 

 

61: Strichman-Almashanu LZ, Lee RS, Onyango PO, Perlman E, Flam F, Frieman MB,

Feinberg AP. A genome-wide screen for normally methylated human CpG islands that

can identify novel imprinted genes. Genome Res. 2002 Apr;12(4):543-54. PubMed

PMID: 11932239; PubMed Central PMCID: PMC187522.

 

 

62: Frieman M, Chen ZJ, Saez-Vasquez J, Shen LA, Pikaard CS. RNA polymerase I

transcription in a Brassica interspecific hybrid and its progenitors: Tests of

transcription factor involvement in nucleolar dominance. Genetics. 1999

May;152(1):451-60. PubMed PMID: 10224274; PubMed Central PMCID: PMC1460595.

 

 

 

Research Interests

1.  MERS Coronavirus Pathogenesis

The emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012 as the second highly pathogenic Coronavirus to emerge in the 21st century. Extending our work on innate immunity, host response and pathogenesis from SARS-CoV to MERS-CoV we have identified novel IFN antagonists of MERS-CoV. Using similar technologies we had developed for SARS-CoV, we rapidly screened and identified several IFN antagonists of MERS-CoV, publishing on the mechanism of action for ORF4b. Interestingly, ORF4b from MERS-CoV, and the related hCoV-HKU4 and hCoV-HKU5, all are IFN antagonists and function similarly to block Interferon induction. Developing MERS-CoV pathogenesis studies has been hampered by our finding that MERS-CoV does not replicate in mice. We have developed a transgenic mouse expressing the human homologue of the MERS-CoV receptor (hDPP4) in place of the mouse DPP4 gene and used this model to show an anti-MERS Spike monoclonal antibody can protect mice from infection.

    Coleman CM, Frieman MB. Emergence of the Middle East respiratory syndrome coronavirus. PLoS Pathog. 2013;9(9):e1003595. PubMed PMID: 24039577; PubMed Central PMCID: PMC3764217.

      Coleman CM, Matthews KL, Goicochea L, Frieman MB. Wild-type and innate immune-deficient mice are not susceptible to the Middle East respiratory syndrome coronavirus. J Gen Virol. 2014 Feb;95(Pt 2):408-12. PubMed PMID: 24197535; PubMed Central PMCID: PMC3917065.

        Matthews KL, Coleman CM, van der Meer Y, Snijder EJ, Frieman MB. The ORF4b-encoded accessory proteins of Middle East respiratory syndrome coronavirus and two related bat coronaviruses localize to the nucleus and inhibit innate immune signalling. J Gen Virol. 2014 Apr;95(Pt 4):874-82. PubMed PMID: 24443473; PubMed Central PMCID: PMC3973478.

          Pascal KE, Coleman CM, Mujica AO, Kamat V, Badithe A, Fairhurst J, Hunt C, Strein J, Berrebi A, Sisk JM, Matthews KL, Babb R, Chen G, Lai KM, Huang TT, Olson W, Yancopoulos GD, Stahl N, Frieman MB, Kyratsous CA. Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection. Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):8738-43. PubMed PMID: 26124093; PubMed Central PMCID: PMC4507189

           

          2.  SARS Coronavirus Pathogenesis

          The emergence of SARS-CoV in 2003 highlighted the lack of knowledge on coronavirus pathogenesis while at the same time, allowed for deeper understanding of the host response to a novel virus. Our studies were focused on understanding the host response to SARS-CoV infection and how the virus modulates this response. Wildtype SARS-CoV is 10% lethal in humans but not in mice. During this time a mouse adapted SARS-CoV was produced in collaboration with Dr. Subbarhoa that causes lethal disease in mice, which I extensively characterized to identify which of the genomic changes responsible for lethal disease. Using both a reverse genetic system for SARS-CoV and newly developing deep sequencing technologies, we identified SARS-CoV mutations that effect pathogenesis, host transcriptome changes that occur during infection, the alterations in small RNAs and non-coding RNAs during infection and how the cytokine response and its effect on pathogenesis change with the age of mice during SARS-CoV infection.

          Rockx B, Baas T, Zornetzer GA, Haagmans B, Sheahan T, Frieman M, Dyer MD, Teal TH, Proll S, van den Brand J, Baric R, Katze MG. Early upregulation of acute respiratory distress syndrome-associated cytokines promotes lethal disease in an aged-mouse model of severe acute respiratory syndrome coronavirus infection. J Virol. 2009 Jul;83(14):7062-74. PubMed PMID: 19420084; PubMed Central PMCID: PMC2704758.

          Peng X, Gralinski L, Armour CD, Ferris MT, Thomas MJ, Proll S, Bradel-Tretheway BG, Korth MJ, Castle JC, Biery MC, Bouzek HK, Haynor DR, Frieman MB, Heise M, Raymond CK, Baric RS, Katze MG. Unique signatures of long noncoding RNA expression in response to virus infection and altered innate immune signaling. MBio. 2010 Oct 26;1(5)PubMed PMID: 20978541; PubMed Central PMCID: PMC2962437.

          Peng X, Gralinski L, Ferris MT, Frieman MB, Thomas MJ, Proll S, Korth MJ, Tisoncik JR, Heise M, Luo S, Schroth GP, Tumpey TM, Li C, Kawaoka Y, Baric RS, Katze MG. Integrative deep sequencing of the mouse lung transcriptome reveals differential expression of diverse classes of small RNAs in response to respiratory virus infection. MBio. 2011;2(6)PubMed PMID: 22086488; PubMed Central PMCID: PMC3221602.

          Frieman M, Yount B, Agnihothram S, Page C, Donaldson E, Roberts A, Vogel L, Woodruff B, Scorpio D, Subbarao K, Baric RS. Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease. J Virol. 2012 Jan;86(2):884-97. PubMed PMID: 22072787; PubMed Central PMCID: PMC3255850

          3.  Coronavirus Therapeutics

          Our current MERS-CoV focus is on therapeutics that can inhibit both MERS-CoV and SARS-CoV. Using both in vitro and in vivo experiments, we are identifying and characterizing various therapeutics for translational application. In the 10 years between the emergence of SARS-CoV and MERS-CoV there are no approved therapeutics for use in people. We are filling that gap with platforms of FDA approved drugs, monoclonal and polyclonal antibodies and vaccines that can be used for MERS-CoV or potentially the next emerging Coronavirus. Testing of several hundred FDA approved drugs identified over two dozen drugs that block both viruses in vitro. In addition to drug identification, we have developed a novel Spike nanoparticle vaccine that produces anti-MERS neutralizing antibodies in mice, human monoclonal antibodies that block infection in cells and our novel MERS-CoV mouse model and a polyclonal antibody product from transchromosomic bovines (contain entire hIgG locus) that inhibits MERS-CoV infection in vitro and in vivo (Accepted 1/2016 in Science Translational Medicine).

          Hart BJ, Dyall J, Postnikova E, Zhou H, Kindrachuk J, Johnson RF, Olinger GG Jr, Frieman MB, Holbrook MR, Jahrling PB, Hensley L. Interferon-β and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays. J Gen Virol. 2014 Mar;95(Pt 3):571-7. PubMed PMID: 24323636; PubMed Central PMCID: PMC3929173.

          Coleman CM, Liu YV, Mu H, Taylor JK, Massare M, Flyer DC, Glenn GM, Smith GE, Frieman MB. Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in mice. Vaccine. 2014 May 30;32(26):3169-74. PubMed PMID: 24736006; PubMed Central PMCID: PMC4058772.

          Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J, Johnson RF, Olinger GG Jr, Jahrling PB, Laidlaw M, Johansen LM, Lear-Rooney CM, Glass PJ, Hensley LE, Frieman MB. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93. PubMed PMID: 24841273; PubMed Central PMCID: PMC4136000.

          Coleman CM, Sisk JM, Mingo RM, Nelson EA, White JM, Frieman MB. Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion. J Virol. 2016 Sep, 12;90(19):8924-33. doi: 10.1128/JVI.01429-16. Print 2016 Oct 1. PubMed PMID:27466418.

           4. Zika virus Therapeutics

          We have utilized our novel drug screening platform in yeast to identify viral protein targets for drug screening.  The Zika virus is an emerging pathogen for which little is known about its biology, replication, pathogenesis or inhibitory therapeutics.  We are identifying and validating drugs identified in yeast for their inhibition of Zika virus in culture.  Then using the recently developed mouse models for Zika virus pathogenesis we will screen these in vitro identified drugs for in vivo activity. 

          Awards and Affiliations

          Awards and Honors

          1994-1997                HHMI Summer Research Fellowship to support research in the lab of Dr. Craig Pikaard (Washington Univ. in St. Louis)

          1995-1997                HHMI Summer Research Travel Award (Wash Univ. in St. Louis)

          2007                        UNC-CH Post-doctoral Award for Research Excellence

          2007                        ASV Post-doctoral Travel Scholarship (UNC-CH)

          2010                        Teaching Commendation for Host Defenses and Infectious Diseases (UMSOM)

          2012                        Teaching Commendation for Host Defenses and Infectious Diseases (UMSOM)

          2014                        Winner, Daily Record, Innovator of the Year

          2015                        Teaching Commendation for Host Defenses and Infectious Diseases (UMSOM)