Ivan Martinez, PhD

Associate Professor

Organization:

West Virginia University WVU Cancer Institute

Department:

WVU Cancer Institute Research Laboratories

Classification:

Faculty

Associate Professor

Organization:

West Virginia University School of Medicine

Department:

Microbiology, Immunology & Cell Biology

Classification:

Faculty

Member

Organization:

West Virginia University WVU Cancer Institute

Department:

WVU Cancer Institute Research Programs

Classification:

Faculty

• LGG, Postdoctoral Fellowship, Yale University, School of Medicine, 2012
• PhD, University of Pittsburgh, School of Medicine, 2007
• MSc, National Autonomous University of Mexico (Universidad Nacional Autonoma de Mexico, UNAM), 2001
• BS, National Autonomous University of Mexico (Universidad Nacional Autonoma de Mexico, UNAM), 1998

Madajewski B, Boatman MA, Martinez I, Carter JH, Bey EA. NAD(P)H Quinone Oxidoreductase-1 Expression Promotes Self-Renewal and Therapeutic Resistance in Non-Small Cell Lung Cancer. Genes (Basel). 2023 Feb 28;14(3):607.  doi: 10.3390/genes14030607. PMID: 36980879  PMCID: PMC10047941  DOI: 10.3390/genes14030607.

Lee SM , Winters MT, Martinez I, Slack FJ. Small regulatory RNAs: from bench to bedside - a keystone symposia meeting report. RNA Biol. 2023 Jan;20(1):136-139.  doi: 10.1080/15476286.2023.2196046. PMID: 37016725  PMCID: PMC10078130  DOI: 10.1080/15476286.2023.2196046.

Yu HG, Sizemore G, Martinez I, Perrotta P. Inhibition of SARS-CoV-2 Viral Channel Activity Using FDA-Approved Channel Modulators Independent of Variants. Biomolecules. 2022 Nov; 12(11): 1673. doi: 10.3390/biom12111673. PMCID: PMC9687591. PMID: 36421688.

Lee KS, Russ BP, Wong TY, Horspool AM, Winters MT, Barbier M, Bevere JR, Martinez I, Damron FH, Cyphert HA. Obesity and metabolic dysfunction drive sex-associated differential disease profiles in hACE2-mice challenged with SARS-CoV-2. iScience. 2022 Oct 21;25(10):105038. doi: 10.1016/j.isci.2022.105038. Epub 2022 Sep 2. PubMed PMID: 36068847; PubMed Central PMCID: PMC9436780.

Esposito R, Polidori T, Meise DF, Pulido-Quetglas C, Chouvardas P, Forster S, Schaerer P, Kobel A, Schlatter J, Kerkhof E, Roemmele M, Rice ES, Zhu L, Lanzós A, Guillen-Ramirez HA, Basile G, Carrozzo I, Vancura A, Ullrich S, Andrades A, Harvey D, Medina PP, Ma PC, Haefliger S, Wang X, Martinez I, Ochsenbein AF, Riether C, Johnson R. Multi-hallmark long noncoding RNA maps reveal non-small cell lung cancer vulnerabilities. Cell Genom. 2022 Aug 22;2(9):100171.  doi: 10.1016/j.xgen.2022.100171.  eCollection 2022 Sep 14. PMID: 36778670  PMCID: PMC9903773.

Wong TY, Russ BP, Lee KS, Miller OA, Kang J, Cooper M, Winters MT, Rodriguez-Aponte SA, Dalvie NC, Johnston RS, Rader NA, Wong ZY, Cyphert HA, Martinez I, Shaligram U, Batwal S, Lothe R, Chandrasekaran R, Nagar G, Rajurkar M, Rao H, Bevere JR, Barbier M, Love JC, Damron FH. RBD-VLP Vaccines Adjuvanted with Alum or SWE Protect K18-hACE2 Mice against SARS-CoV-2 VOC Challenge. mSphere. 2022 Aug 31;7(4):e0024322. doi: 10.1128/msphere.00243-22. Epub 2022 Aug 15. PubMed PMID: 35968964; PubMed Central PMCID: PMC9429941.

Lee KS, Wong TY, Russ BP, Horspool AM, Miller OA, Rader NA, Givi JP, Winters MT, Wong ZYA, Cyphert HA, Denvir J, Stoilov P, Barbier M, Roan NR, Amin MS, Martinez I, Bevere JR, Damron FH. SARS-CoV-2 Delta variant induces enhanced pathology and inflammatory responses in K18-hACE2 mice. PLoS One.2022 Aug 29;17(8):e0273430. doi: 10.1371/journal.pone.0273430. eCollection 2022. PubMed PMID: 36037222; PubMed Central PMCID: PMC9423646.

Barbier M, Lee KS, Vikharankar MS, Rajpathak SN, Kadam N, Wong TY, Russ BP, Cyphert HA, Miller OA, Rader NA, Cooper M, Kang J, Sen-Kilic E, Wong ZY, Winters MT, Bevere JR, Martinez I, Devarumath R, Shaligram US, Damron FH. Passive immunization with equine RBD-specific Fab protects K18-hACE2-mice against Alpha or Beta variants of SARS-CoV-2. Front Immunol. 2022 Aug 15;13:948431. doi: 10.3389/fimmu.2022.948431. eCollection 2022. PubMed PMID: 36091051; PubMed Central PMCID: PMC9450042.

Wong TY, Horspool AM, Russ BP, Ye C, Lee KS, Winters MT, Bevere JR, Miller OA, Rader NA, Cooper M, Kieffer T, Sourimant J, Greninger AL, Plemper RK, Denvir J, Cyphert HA, Barbier M, Torrelles JB, Martinez I, Martinez-Sobrido L, Damron FH. Evaluating Antibody Mediated Protection against Alpha, Beta, and Delta SARS-CoV-2 Variants of Concern in K18-hACE2 Transgenic Mice. J Virol. 2022 Mar 23;96(6):e0218421. doi: 10.1128/jvi.02184-21. Epub 2022 Jan 26. PubMed PMID: 35080423; PubMed Central PMCID: PMC8941865.

Wong TY, Lee KS, Russ BP, Horspool AM, Kang J, Winters MT, Allison Wolf M, Rader NA, Miller OA, Shiflett M, Izac J, Varisco D, Sen-Kilic E, Cunningham C, Cooper M, Cyphert HA, Barbier M, Martinez I, Bevere JR, Ernst RK, Damron FH. Intranasal administration of BReC-CoV-2 COVID-19 vaccine protects K18-hACE2 mice against lethal SARS-CoV-2 challenge. NPJ Vaccines. 2022 Mar 14;7(1):36. doi: 10.1038/s41541-022-00451-7. PubMed PMID: 35288576; PubMed Central PMCID: PMC8921182.

McCall, J.L., Varney, M.E., Rice, E., Dziadowicz, S.A., Hall, C., Blethen, K. Hu, G., Barnett, J.B., Martinez, I. Prenatal cadmium exposure alters proliferation in mouse CD4+ T cells via LncRNA Snhg7. Front Immunol. 2022 Jan 11:12:720635.  doi: 10.3389/fimmu.2021.720635.  eCollection 2021. PMID: 35087510  PMCID: PMC8786704.

Yekelchyk M, Madan E, Wilhelm J, Short KR, Palma AM, Liao L, Camacho D, Nkadori E, Winters MT, Rice ES, Rolim I, Cruz-Duarte R, Pelham CJ, Nagane M, Gupta K, Chaudhary S, Braun T, Pillappa R, Parker MS, Menter T, Matter M, Haslbauer JD, Tolnay M, Galior KD, Matkwoskyj KA, McGregor SM, Muller LK, Rakha EA, Lopez-Beltran A, Drapkin R, Ackermann M, Fisher PB, Grossman SR, Godwin AK, Kulasinghe A, Martinez I, Marsh CB, Tang B, Wicha MS, Won KJ, Tzankov A, Moreno E, Gogna R. Flower lose, a cell fitness marker, predicts COVID-19 prognosis. EMBO Mol Med. 2021 Nov 8;13(11):e13714. doi: 10.15252/emmm.202013714. Epub 2021 Oct 18. PubMed PMID: 34661368; PubMed Central PMCID: PMC8573598.

Horspool AM, Ye C, Wong TY, Russ BP, Lee KS, Winters MT, Bevere JR, Kieffer T, Martinez I, Sourimant J, Greninger A, Plemper RK, Denvir J, Cyphert HA, Torrelles J, Martinez-Sobrido L, Damron FH. SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern induce lethal disease in K18-hACE2 transgenic mice despite convalescent plasma therapy. bioRxiv. 2021 May 5;. doi: 10.1101/2021.05.05.442784. PubMed PMID: 33972945; PubMed Central PMCID: PMC8109207.

Horspool AM, Kieffer T, Russ BP, Dejong MA, Wolf AM, Karakiozis JM, Hickey BJ, Fagone P, Tacker DH, Bevere JR, Martinez I, Barbier M, Perrotta PL, Damron HF. (2021) Interplay of antibody and cytokine production reveals CXCL-13 as a potential novel biomarker of lethal SARS-CoV-2 infection. mSphere Jan 20;6(1):e01324-20.  doi: 10.1128/mSphere.01324-20.

He, Z., Liu, X., Wu, F., Wu, S., Rankin, G.O., Martinez, I., Rojanasakul, Y., 5 Chen, Y.C. (2021) Gallic Acid Induces S and G2 Phase Arrest and Apoptosis in Human Ovarian Cancer Cells In Vitro. Appl Sci (Basel) May 1;11(9):3807.  doi: 10.3390/app11093807.

He, Z., Wu, S., Lin, J., Booth, A., Rankin, G.O., Martinez, I., Chen, Y.C. (2020) Polyphenols Extracted from Chinese Hickory ( Carya cathayensis) Promote Apoptosis and Inhibit Proliferation through the p53-Dependent Intrinsic and HIF-1α-VEGF Pathways in Ovarian Cancer Cells. Appl Sci (Basel) Dec 1;10(23):8615.  doi: 10.3390/app10238615.           

Brownmiller, T., Juric, J.A., Ivey, A.D., Harvey, B.M., Westemeier, E.S., Winters, M.T., Stevens, A.M., Stanley, A.N., Hayes, K.E., Sprowls, S.A., Gatesman Ammer, A.S., Walker, M., Bey, E.A., Wu, X., Lim, Z.F., Zhu, L., Wen, S., Hu, G., Ma, P.C., Martinez I. (2020) Y Chromosome LncRNA are involved in Radiation Response of Male Non-Small Cell Lung Cancer Cells. Cancer Research Jul 2:canres.4032.2019. doi: 10.1158/0008-5472.CAN-19-4032.

Hathaway, Q.A., Taylor, A.D., Kunovac, A., Pinti, M.V., Newman, M.S., Cook, C.C., Winters, M.T., Westemeier, E., Fink, G.K., Durr, A.J., Shepherd, D.L., Robart, A.R., Martinez, I., Hollander, J.M. (2020) Mitochondrial Import of Malat1 Regulates Cardiac Mitochondrial Function in Type 2 Diabetes Mellitus through Interaction with MicroRNA-23b. Research Square Preprint. DOI: 10.21203/rs.3.rs-127504/v1.

Barr, J.A., Hayes, K.E., Brownmiller, T., Harold, A., Jagannathan, R., Lockman, P., Khan, S.A., Martinez, I. Long non-coding RNA FAM83H-AS1 is regulated by human papillomavirus 16 E6 independently of p53 in cervical cancer cells. Scientific Reports 2019 Mar 6;9(1):3662.

Hayes, K.E., Barr, J.A., Xie, M., Steitz, J.A., Martinez, I. (2018) Immunoprecipitation of Tri-methylated Capped RNA. Bio-protocol. 8(03):bio-protocol.org/e2717

Martinez, I., Hayes, K.E., Barr, J.A., Harold, A., Xie, M., Bukhari, S.I.A., Vasudevan, S., Steitz, J.A., DiMaio, D. (2017) An Exportin-1-dependent microRNA Biogenesis Pathway During Human Cell Quiescence. Proc Natl Acad Sci U S A. 114(25):E4961-E4970.

Shepherd D, Hathaway Q, Pinti M, Nichols C, Durr A, Sreekumar S, Hughes K, Stine S, Martinez I, Hollander J. Exploring the mitochondrial microRNA import pathway through Polynucleotide Phosphorylase (PNPase). J Mol Cell Cardiol. 2017; Sep (110): 15-25.

Moses BS, Evans R, Slone WL, Piktel D, Martinez I, Craig MD, Gibson LF. Bone Marrow Microenvironment Niche Regulates miR-221/222 in Acute Lymphoblastic Leukemia. Mol Cancer Res. 2016;14(10):909-919.

Jagannathan R, Thapa D, Nichols CE, Shepherd DL, Stricker JC, Croston TL, Baseler WA, Lewis SE, Martinez I, Hollander JM. Translational Regulation of the Mitochondrial Genome Following Redistribution of Mitochondrial MicroRNA in the Diabetic Heart. Circulation. Cardiovascular genetics. 2015; 8(6):785-802.

Hu, Z., Klein, J.D., Mitch, W.E., Zhang, L., Martinez, I., and Wang, X.H. (2014) MicroRNA-29 induces cellular senescence in aging muscle through multiple signaling pathways. Aging (Albany NY) 3:160-175

Unlu, S., Tang, S., Wang, E., Martinez, I., Tang, D., Bianchi, M., Zeh, H., and Lotze, M.T. (2012) Damage associated molecular pattern molecule-induced microRNAs (DAMPmiRs) induction in human peripheral blood mononuclear cells. PLoS One. 2012;7(6):e38899.

Martinez, I., Cazalla, D., Almstead, LL., Steitz, JA., and DiMaio, D. (2011) miR-29 and miR-30 Regulate B-Myb Expression During Cellular Senescence. Proc Natl Acad Sci U S A 108: 522-527.

Martinez, I., and DiMaio, D. (2011) B-Myb, Cancer, Senescence, and MicroRNAs. Cancer Res 71:5370-5373.

Martinez, I., Almstead, LL., and DiMaio, D. (2011) MicroRNAs and Senescence. Aging (Albany NY) 3:77-78.

Martinez, I., Gardiner, A.S., Board, K.F., Monzon, F.A., Edwards, R.P., and Khan, S.A. (2008) Human papillomavirus type 16 reduces the expression of microRNA-218 in cervical carcinoma cells. Oncogene 27: 2575-2582.

Martinez, I., Wang, J., Hobson, K.F., Ferris, R.L., and Khan, S.A. (2007) Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas. Eur J Cancer 43: 415-432.

Ferris, R.L., Martinez, I., Sirianni, N., Wang, J., Lopez-Albaitero, A., Gollin, S.M., Johnson, J.T., and Khan, S.A. (2005) Human papillomavirus 16-associated squamous cell carcinoma of the head and neck (SCCHN): A natural disease model provides insights into viral carcinogenesis. Eur J Cancer 41: 807-815.

Martinez, I., Mantilla, A., Medrano, M.E., Hernandez, R., Hernandez, D.M., Hidalgo, A., Lazos, M., Santiago, H., Gonzalez, G., Hidalgo, A., and Salcedo, M. (2001) High prevalence of RET tyrosine kinase activation in Mexican patients with papillary thyroid carcinomas. Endocr Pathol 12: 113-123.

Hidalgo, A., Medrano, M., Rodriguez, S., Franco, C., Martinez, I., Benitez, L., and Salcedo, M. (1998) Presence of the 918 mutation in the RET proto-oncogene in a Mexican patient with multiple endocrine neoplasia Type 2B. J Exp Clin Cancer Res 17: 149-152.

Academic Interest

In the last seven decades, most of our biomedical research has been focused on the importance of protein coding genes and their mutations at the DNA level. However, after the human genome was completely sequenced in 2003, researchers discovered that only 1-2% of our genome encodes for proteins while most of the human genome (98%) expresses RNAs known as non-coding RNAs (ncRNAs) which, as the name implies, do not encode for proteins. This “universe” of ncRNAs contains hundredths of thousands of RNA molecules with unknown functions, leading researchers to call them the “dark matter” of biology.

The interest of my laboratory is to understand the importance of ncRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular non-coding RNAs (circRNAs), in the process of carcinogenesis and viral infections. A few years ago, my laboratory published the identification of an oncogenic lncRNA (FAM83H-AS1) overexpress in Human Papillomavirus type 16 (HPV-16) cervical and head and neck cancers. We found that HPV-16 viral oncogenic protein E6 is responsible of overexpressing FAM83H-AS1 through a p53-independent pathway (Scientific Reports, 2019). Also, our group published the discovery of a family of lncRNAs expressed from the Y chromosome involved in the process or radiation therapy susceptibility in male non-small-cell lung carcinomas (NSCLC). We found that the lnc-SPRY3 family have a dose dependent expression after radiation in radiosensitive NSCLC cell lines but not in radioresistant NSCLC cell lines (Cancer Research, 2020). More recently, we published that prenatal Cadmium (Cd) exposure alters the expression of the lncRNA known as lnc-Snhg7 during T cell activation. We identified that lnc-Snhg7 is overexpressed in Tcells from Cd offspring resulting in the upregulation of GALNT7 protein, via competing endogenous activity of miR-34a (Frontiers in Immunology, 2022). At the beginning of the COVID-19 pandemic and because of my virology background, I became the Co-leader of a group of researchers involved in the development of the COVID-19 PCR test (from in-house reagents to a fully automated testing robot). The development of this test was essential for WVU and the entire State of West Virginia during the COVID-19 pandemic. Also, my group was in charge of manipulating all the SARS-CoV-2 variants in the WVU Biosafety Level 3 (BSL3) laboratory in order to generate in vitro and in vivo experiments. Furthermore, I’m one of two professors at WVU that are member of the World Health Organization (WHO) COVID-19 Animal Models Group.

Media Presentations:

The local newspaper Daily Athenaeum. Spring break trips canceled, WVU continues to monitor coronavirus (March 5th, 2020) 
https://www.thedaonline.com/latest_edition/march/pdf_8960141e-5ea8-11ea-83c3-5f74c9d59ab4.html

The National USA Today newspaper. Why a coronavirus vaccine is more than a year away, despite medical researchers’ progress (March 11th, 2020)
https://www.usatoday.com/in-depth/news/2020/03/09/biotech-international-effort-makes-big-push-for-coronavirus-vaccine/4927298002/

The Spanish newspaper from Barcelona “El Periodico”. La carrera por la vacuna contra el coronavirus (March 19th, 2020)
https://www.elperiodico.com/es/internacional/20200318/carrera-vacuna-coronavirus-china-eeuu-europa-7894445?utm_source=facebook&utm_medium=social&utm_campaign=btn-share&fbclid=IwAR3Nra-CSirYtKzp3fxOaH67bcRwBTuFGVD-e7KuB7q1V0l96jHOf1hJNhI

Interview in the local TV channel WCHS TV 8 from Charleston, WV (March 24th, 2020)
https://wchstv.com/news/coronavirus/experts-explain-the-quick-spread-of-covid-19

WVU and the Coronavirus Podcast, Episode 2: Vaccine science, RNA viruses, and are they alive? (May 27^th,2020)
https://health.wvu.edu/news/story?headline=episode-2-of-wvu-s-covid-19-podcast-available-now

WVU TODAY E-News. To help West Virginia reopen safely, WVU researchers develop new COVID-19 test (June 11^th, 2020)
https://wvutoday.wvu.edu/stories/2020/06/11/to-help-west-virginia-reopen-safely-wvu-researchers-develop-new-covid-19-tests?utm_source=MOUNTAINEER+ENEWS&utm_campaign=e945a3d32e-RSS_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_02ac3f7274-e945a3d32e-136479085

Interview in the local Radio MetroNews Talkline (June 15^th, 2020; interview start at 27:35)
https://wvmetronews.com/podcast/talkline/

Interview in the local TV channel 5WDTV. WVU researchers develop COVID-19 tests as students prepare to return to campus (June 24^th, 2020)
https://www.wdtv.com/2020/06/24/wvu-researchers-developing-covid-19-tests-as-students-prepare-to-return-to-campus/

Interview in the local TV channel 12WBOY. West Virginia University researchers develop new COVID-19 tests (July 15^th, 2020).
https://www.wboy.com/news/health/coronavirus/west-virginia-university-researchers-develop-new-covid-19-tests/

Interview in the local TV channel WCHS TV 8 from Charleston, WV. Barboursville couple taking part in Pfizer COVID-19 vaccine trial (November 18^th, 2020).
https://wchstv.com/news/local/barboursville-couple-taking-part-in-pfizer-covid-19-vaccine-trial

Interview in the local TV channel WCHS TV 8 from Charleston, WV. Health official discusses COVID-19 vaccines' potential long term side effects (December 21^st, 2020).
https://wchstv.com/news/local/health-official-discusses-covid-19-vaccines-potential-long-term-side-effects

WVU TODAY. ‘Don’t feel like a guinea pig:’ New COVID-19 vaccine is safe, effective (December 22^nd, 2020).
https://wvutoday.wvu.edu/stories/2020/12/22/-don-t-feel-like-a-guinea-pig-new-covid-19-vaccine-is-safe-effective

WVU TODAY. ‘No COVID-19 is good COVID-19': Variants spur WVU scientists to study, mitigate strain outbreaks (February 20^th, 2021).
https://wvutoday.wvu.edu/stories/2021/02/20/-no-covid-19-is-good-covid-19-variants-spur-wvu-scientists-to-study-mitigate-strain-outbreaks

Sara Crile Allen and James Frederick Allen Lung Cancer

Understanding the importance of non-coding RNAs in human papillomavirus-related cancers and models of growth arrest

Twitter: IvanMartinezLab