MARIO ACUNZO

Ricercatore universitario


email: mario.acunzo@vcuhealth.org
telefono: +1 6145994069
edificio: Molecular Medicine Research Building (MMRB)
stanza: 4044

Mario Acunzo, M.S., Ph.D.
VCU Medical Center
1220 E. Broad Street
Molecular Medicine Research Building
Room 4044 – P.O. Box 980456
Richmond VA 23298
Phone (804) 828-7443
E-mail: mario.acunzo@vcuhealth.org
acunzohome@gmail.com


CITIZENSHIP
Italian
American Green Card holder.

LANGUAGE
Fluent in English and Italian.

CURRENT POSITION
Assistant Professor,
Department of Internal Medicine,
Division of Pulmonary Disease and Critical Care Medicine
Virginia Commonwealth University


EDUCATION
Oct 2004: Master of Science (M.S.) in "Biological Sciences" (Laurea in Scienze Biologiche), University of Naples "Federico II,” Italy.
Jan 2008: Ph.D. in Genetics and Molecular Medicine, School of Medicine, University of Naples "Federico II," Italy.

ACADEMIC APPOINTMENTS

2008-2014: Postdoctoral Researcher, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University (OSU), Columbus, Ohio. Mentor: Carlo M Croce, MD.

2014-2017: Research Scientist, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University (OSU), Columbus, OH, USA.


2017-Present: Assistant Professor, Division of Pulmonary Disease and Critical Care
Medicine, Virginia Commonwealth University (VCU), Richmond, VA, USA


CONTRIBUTION TO SCIENCE

During the last decade, I mainly focused my research on the role of small non-coding RNAs in Lung Cancer. As early as 2009, I participated in a research project that uncovered the fundamental role of miR-221 and miR-222 in TRAIL resistance in Non-small Cell Lung Cancer (NSCLC). In 2011, I discovered that miR-130a could induce TRAIL sensitivity in NSCLC by downregulating the MET-induced expression of the miR-221/miR-222 cluster. I also participated in a study on the role of miR-494 as another critical regulator of TRAIL resistance in NSCLC. Finally, in 2013, I uncovered a new crosstalk path between MET and EGFR in NSCLC involving miR-27a and Sprouty2. I served as the primary investigator or co-investigator in all of these studies.
Later, I also dedicated my research to studying genetic aberrations in human Chronic Lymphocytic Leukemia (CLL). In 2014, I characterized a new translocation in a human case of CLL that involves chromosomes 2 and 11, discovering a unique fusion oncogene resulting from the fusion of CXCR4 and MAML2, two critical genes involved in cancer.
Recently, I developed a method to specifically target point-mutated mRNAs such as KRAS employing a specific artificial microRNA design. In addition, I recently focused my research on detecting and profiling the microRNA editing phenomenon and isomiR detection. My group identified the role of microRNA editing on the hypoxia-induced pathway. We also have detected microRNA editing in circulating extracellular vesicles (EVs) of Lung Cancer patients for the first time. I served as a primary investigator or co-corresponding author in all of these studies.


HONORS AND AWARDS

2006-2007: AIRC (Italian Association for Cancer Research) Pre-doctoral Fellowship, Winner.

2018- present: National Center for Advancing Translational Sciences (NCATS), National Institute of Health (NIH), USA, Mentored Career Development Award (KL2), Awardee.

2022 – 2031: National Scientific Qualification (ASN 2021/2023) as associate (fascia II) in the Italian higher education system for the disciplinary field of 05/E2 - Biologia Molecolare (Molecular biology).

2022 – 2031: National Scientific Qualification (ASN 2021/2023) as associate (fascia II) in the Italian higher education system for the disciplinary field of 05/F1 -Biologia Applicata (Experimental Biology).

2022 – 2031: National Scientific Qualification (ASN 2021/2023) as associate (fascia II) in the Italian higher education system for the disciplinary field of 06/A2 -Patologia Generale e Patologia Clinica (Experimental medicine, pathophysiology, and clinical pathology).

2022 – 2031: National Scientific Qualification (ASN 2021/2023) as associate (fascia II) in the Italian higher education system for the disciplinary field of 06/N1 – Scienze delle professioni Sanitarie e delle Tecnologie Mediche (Technology and methodology in medicine and nursing sciences).


MEMBERSHIP IN PROFESSIONAL SOCIETIES

2013- Present: Active member of the American Association of Cancer Research (AACR).

2017- Present: Associate Member of the Massey Cancer Center (MCC) at VCU, Developmental Therapeutics.

2021- present Member of the Clinical and Translational Science Awards (CTSA) Visiting Professorship program, National Institute of Health (NIH), USA.


SCIENTIFIC AND SCHOLARLY ACTIVITIES

Expert Services and Educational Activities:
2007: Teaching assistant in “Animal models of Human Pathology,” School of Biotechnological Sciences, University of Naples “Federico II.”
2008-present: Peer reviewer for international journals:
Oncogene, International Journal of Cell Biology, Scientifica, Clinical Chemistry, JEV, Scientific Reports, and others.
2017-2018: Guest Editor, Frontiers, Research Topic - Epitranscriptomics: The Novel RNA frontier.

2020: Member, MCC Pilot grant review committee.

2020-present Guest Editor, Genes, Special issue: Epitranscriptomics in Cancer Pathogenesis.
2020: Reviewer, Florida Department of Health (FDOH) Biomedical Research Programs -grant study section 2020-21, USA.
2021-present Member of Early Career Reviewer (ECR) program at the Center for Scientific Review (CSR), National Institute of Health (NIH), USA.
2022- present ECR Reviewer, Academic-Industrial Partnerships Research for Cancer Diagnosis and Treatment, panel for scientific review (ZRG1 SBIB-Q 57). National Institute of Health (NIH), USA.

Invited Speaker and Lectures:
2018: Invited speaker, Massey Cancer Center (VCU), Developmental Therapeutics Group, Richmond, VA, USA. Seminars. Title: "Artificial microRNAs as potential Therapeutics in Cancer."

2018: Invited speaker, Cancer Research Retreat 2018, Massey Cancer Center (VCU) Richmond, VA, USA. Title: "Artificial microRNAs as potential therapeutics in Lung Cancer."

2021: Invited speaker, KL2 exchange program at Georgetown University, Washington DC, USA. Title: "New applications for microRNAs as diagnostics and therapeutics in cancer."

Invited roundtable speaker, Ph.D. school- Cellular and Molecular Biology Workshop Universita “Tor Vergata” Rome, Italy. “Deciphering the complexity in neurodegeneration and cancer.”

March 2022: Invited speaker, CTSA Visiting Professorship program, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA. Title: “Emerging Role of microRNAs in Cancer.”


GRANTS AND CONTRACTS

Active:
MicroRNA Editing in Lung Cancer Pathogenesis.
KL2TR002648-02 (PI: Nana-Sinkam/Sanyal) 5/2018-5/2022
NCATS
Role: Awardee
We will determine whether edited microRNAs drive progression in lung cancer by using comprehensive bioinformatic analysis coupled with Next Generation Sequencing (NGS) data.
Completed in the last three years:
DOIM Pilot grant (PI: Mario Acunzo) August 1, 2017 – Dec 1, 2019
Role: PI
DOIM VCU

VCU Johnson Center for Research Grant (PI: Samira Shojaee) July 1, 2018 – June 30, 2019
Extracellular Vesicle MiRNA in benign and malignant effusions.
Role: co-I

TEACHING AND MENTORING ACTIVITY

Academic Board member:

2020 –present: Academic Board (external member), Ph.D. school in Molecular Medicine University of Rome “La Sapienza.” Italy.

Lecturer:
2019: Cancer Biology course (Bio 450), The Virginia Commonwealth University (VCU), Richmond, VA, USA.

Research Supervisor:

Giovanni Nigita, PhD
Giovanni is a research scientist at the Ohio State University under the supervision of Dr. Carlo Croce. He is a bioinformatician, and I trained him on the biological aspect of his work. He is a successful researcher and an expert in NGS data analysis. We are now productive collaborators; we have recently co-authored several papers.

Luisa Tommasello, PhD
Luisa is a postdoctoral researcher at The Ohio State University. She is under the guidance of Dr. Carlo Croce. I am currently mentoring Luisa to study the microRNAs' post-transcriptional regulation mechanisms in lung cancer.

Daniel del valle Morales, PhD
Daniel is a postdoctoral researcher at Virginia Commonwealth University. He is under the guidance of Dr. Nana-Sinkam. I am currently mentoring Daniel to study how epitranscriptomics impact the RNA 5’ capping. I am his mentor for the project entitled "Epitranscriptomic regulation of Capping Enzyme by METTL3". Daniel achieved the "Postdoctoral Independent Research Award” (PIRA) thanks to this project.

Valentina Chiadini, MS, Ph.D
She has been under my guidance from July and December 2016 when I was at the OSU. I helped her learn microRNA biology and profile microRNAs by nanostring technology in osteosarcoma patients.

Luigi Fattore, MS, Ph.D.
I mentored Luigi in two different periods (May 2014 – Nov. 2014) (Oct 2016 – Dec. 2016) while at the OSU. I mentored him on the biological role of microRNAs in cancer. He successfully applied this training, publishing several manuscripts in journals with a high Impact Factor. Thanks to this productive mentoring, we co-authored several manuscripts.

Yuntao Dai, Ph.D. student
I mentored Yuntao at the OSU (Sept 2014 - Ago 2015). He produced interesting data profiling in a CLL mouse model thanks to my mentoring. As a result, he successfully graduated with a Ph.D. in 2016.

Michela Saviana, MS (Ph.D. student)
I have been mentoring Michela since March 2019 while here at VCU. I am supervising her study on finding novel circulating biomarkers for SCLC.

Marika Vitiello, MS
I mentored Marika only for three months (Sept. 2014 – Dec 2014) while at the OSU. However, Marika produced interesting results despite the short training as co-authors in Nucleic Acids Res. (2016).

Melissa Rodewald, student
I mentored Melissa from May 2016 to Oct 2016 while at OSU. I trained her on the basic lab bench techniques. Melissa has now been accepted to OSU Medical School.

Taruni Maganti, student
I mentored Taruni from May 2019 to Oct 2019 while here at VCU. I trained her in the introductory wet lab. Techniques.


BOOKS

microRNA expression in cancer.
Nana-Sinkam SP, ACUNZO M, Croce CM.
Holland-Frey Cancer Medicine 9th edition.
Chapter 9, 2016.

microRNA expression in cancer.
Nana-Sinkam SP, ACUNZO M, Croce CM.
Holland-Frey Cancer Medicine 10th edition.
Chapter 9, In preparation.


PEER-REVIEWED PUBLICATIONS

1) R Distefano, G Nigita, P Le, G Romano, M Acunzo*, P Nana-Sinkam*. Disparities in Lung Cancer: miRNA Isoform Characterization in Lung Adenocarcinoma. Cancers 14 (3), 773. PMCID: pending.
*These authors have contributed equally to this work

2) Saviana M, Romano G, Le P, Acunzo M, Nana-Sinkam P. Extracellular Vesicles in Lung Cancer Metastasis and Their Clinical Applications. Cancers (Basel). 2021 PMCID: PMC8616161.

3) Marceca GP, Distefano R, Tomasello L, Lagana A, Russo F, Calore F, Romano G, Bagnoli M, Gasparini P, Ferro A, Acunzo M, Ma Q, Croce CM, Nigita G. MiREDiBase, a manually curated database of validated and putative editing events in microRNAs. Sci Data. 2021 PMCID: PMC8338996.

4) Acunzo M, Nana-Sinkam P. Functional Gene Variants in Chronic Obstructive Pulmonary Disease: The Search Continues. Am J Respir Cell Mol Biol. 2021 PMCID: PMC8320122.

5) Marceca GP, Tomasello L, Distefano R, Acunzo M, Croce CM, Nigita G. Detecting and Characterizing A-To-I microRNA Editing in Cancer. Cancers (Basel). 2021 PMCID: PMC8038323.

6) Romano G, Acunzo M, Nana-Sinkam P. microRNAs as Novel Therapeutics in Cancer. Cancers (Basel). 2021 PMCID: PMC8037786.

7) Le P, Romano G, Nana-Sinkam P, Acunzo M. Non-Coding RNAs in Cancer Diagnosis and Therapy: Focus on Lung Cancer. Cancers (Basel). 2021 PMCID: PMC8003033.

8) Romano G, Nigita G, Calore F, Saviana M, Le P, Croce CM, Acunzo M*, Nana-Sinkam P*. MiR-124a Regulates Extracellular Vesicle Release by Targeting GTPase Rabs in Lung Cancer. Front Oncol. 2020 PMCID: PMC7469878.
*These authors have contributed equally to this work

9) Romano G, Saviana M, Le P, Li H, Micalo L, Nigita G, Acunzo M, Nana-Sinkam P. Non-Coding RNA Editing in Cancer Pathogenesis. Cancers (Basel). 2020 PMCID: PMC7408896.

10) Fattore L, Ruggiero CF, Pisanu ME, Liguoro D, Cerri A, Costantini S, Capone F, Acunzo M, Romano G, Nigita G, Mallardo D, Ragone C, Carriero MV, Budillon A, Botti G, Ascierto PA, Mancini R, Ciliberto G. Reprogramming miRNAs global expression orchestrates development of drug resistance in BRAF mutated melanoma. Cell Death Differ. 2019 PMCID: PMC6748102.

11) Nigita G, Marceca GP, Tomasello L, Distefano R, Calore F, Veneziano D, Romano G, Nana-Sinkam SP, Acunzo M, Croce CM. ncRNA Editing: Functional Characterization and Computational Resources. Methods Mol Biol. 2019 PMID: 30635893.

12) Distefano R, Nigita G, Veneziano D, Romano G, Croce CM, Acunzo M. isoTar: Consensus Target Prediction with Enrichment Analysis for MicroRNAs Harboring Editing Sites and Other Variations. Methods Mol Biol. 2019 PMCID: PMC8022917.

13) Nigita G, Acunzo M, Cho WCS, Croce CM. Editorial: Epitranscriptomics: The Novel RNA Frontier. Front Bioeng Biotechnol. 2018 PMCID: PMC6288354.

14) Nigita G, Distefano R, Veneziano D, Romano G, Rahman M, Wang K, Pass H, Croce CM, Acunzo M*, Nana-Sinkam P*. Tissue and exosomal miRNA editing in Non-Small Cell Lung Cancer. Sci Rep. 2018 PMCID: PMC6033928.
*These authors have contributed equally to this work

15) Nana-Sinkam SP, Acunzo M, Croce CM, Wang K. Extracellular Vesicle Biology in the Pathogenesis of Lung Disease. Am J Respir Crit Care Med. 2017 PMCID: PMC5754438.

16) Lee TJ, Yoo JY, Shu D, Li H, Zhang J, Yu JG, Jaime-Ramirez AC, Acunzo M, Romano G, Cui R, Sun HL, Luo Z, Old M, Kaur B, Guo P, Croce CM. RNA Nanoparticle-Based Targeted Therapy for Glioblastoma through Inhibition of Oncogenic miR-21. Mol Ther. 2017 PMCID: PMC5498802.

17) Acunzo M*, Romano G*, Nigita G, Veneziano D, Fattore L, Laganà A, Zanesi N, Fadda P, Fassan M, Rizzotto L, Kladney R, Coppola V, Croce CM. Selective targeting of point-mutated KRAS through artificial microRNAs. Proc Natl Acad Sci U S A. 2017 PMCID: PMC5448175.
*These authors have contributed equally to this work

18) Romano G, Veneziano D, Acunzo M, Croce CM. Small non-coding RNA and cancer. Carcinogenesis. 2017 PMCID: PMC6248440.

19) Barger JF, Rahman MA, Jackson D, Acunzo M, Nana-Sinkam SP. Extracellular miRNAs as biomarkers in cancer. Food Chem Toxicol. 2016 PMCID: PMC5086286.

20) Fattore L, Mancini R, Acunzo M, Romano G, Laganà A, Pisanu ME, Malpicci D, Madonna G, Mallardo D, Capone M, Fulciniti F, Mazzucchelli L, Botti G, Croce CM, Ascierto PA, Ciliberto G. miR-579-3p controls melanoma progression and resistance to target therapy. Proc Natl Acad Sci U S A. 2016 PMCID: PMC5003278.

21) Alaimo S, Giugno R, Acunzo M, Veneziano D, Ferro A, Pulvirenti A. Post-transcriptional knowledge in pathway analysis increases the accuracy of phenotypes classification. Oncotarget. 2016 PMCID: PMC5342365.

22) Nigita G*, Acunzo M*, Romano G, Veneziano D, Laganà A, Vitiello M, Wernicke D, Ferro A, Croce CM. microRNA editing in seed region aligns with cellular changes in hypoxic conditions. Nucleic Acids Res. 2016 PMCID: PMC4994866.
*These authors have contributed equally to this work

23) Rossi M, Colecchia D, Ilardi G, Acunzo M, Nigita G, Sasdelli F, Celetti A, Strambi A, Staibano S, Croce CM, Chiariello M. MAPK15 upregulation promotes cell proliferation and prevents DNA damage in male germ cell tumors. Oncotarget. 2016 PMCID: PMC4991506.

24) Acunzo M, Croce CM. Downregulation of miR-15a and miR-16-1 at 13q14 in Chronic Lymphocytic Leukemia. Clin Chem. 2016 PMCID: PMC4963818.

25) Balatti V, Acunzo M, Pekarky Y, Croce CM. Novel mechanisms of regulation of miRNAs in CLL. Trends Cancer. 2016 PMCID: PMC4874335.

26) Drusco A, Bottoni A, Laganà A, Acunzo M, Fassan M, Cascione L, Antenucci A, Kumchala P, Vicentini C, Gardiman MP, Alder H, Carosi MA, Ammirati M, Gherardi S, Luscrì M, Carapella C, Zanesi N, Croce CM. A differentially expressed set of microRNAs in cerebro-spinal fluid (CSF) can diagnose CNS malignancies. Oncotarget. 2015 PMCID: PMC4673232.

27) Acunzo M, Croce CM. MicroRNA in Cancer and Cachexia--A Mini-Review. J Infect Dis. 2015 PMCID: PMC4574551.

28) Acunzo M, Romano G, Wernicke D, Croce CM. MicroRNA and cancer--a brief overview. Adv Biol Regul. 2015 Review. PMID: 25294678.

29) Rahman M, Lovat F, Romano G, Calore F, Acunzo M, Bell EH, Nana-Sinkam P. miR-15b/16-2 regulates factors that promote p53 phosphorylation and augments the DNA damage response following radiation in the lung. J Biol Chem. 2014 PMCID: PMC4176210.

30) Acunzo M*, Romano G*, Wernicke D, Balatti V, Rassenti LZ, dell'Aquila M, Kipps TJ, Pekarsky Y, Croce CM. Translocation t(2;11) in CLL cells results in CXCR4/MAML2 fusion oncogene. Blood. 2014 PMCID: PMC4093682.
*These authors have contributed equally to this work
31) Drusco A, Nuovo GJ, Zanesi N, Di Leva G, Pichiorri F, Volinia S, Fernandez C, Antenucci A, Costinean S, Bottoni A, Rosito IA, Liu CG, Burch A, Acunzo M, Pekarsky Y, Alder H, Ciardi A, Croce CM. MicroRNA profiles discriminate among colon cancer metastasis. PLoS One. 2014 PMCID: PMC4055753.

32) Laganà A*, Acunzo M*, Romano G, Pulvirenti A, Veneziano D, Cascione L, Giugno R, Gasparini P, Shasha D, Ferro A, Croce CM. miR-Synth: a computational resource for the design of multi-site multi-target synthetic miRNAs. Nucleic Acids Res. 2014 PMCID: PMC4027198.
*These authors have contributed equally to this work
33) Galli R, Paone A, Fabbri M, Zanesi N, Calore F, Cascione L, Acunzo M, Stoppacciaro A, Tubaro A, Lovat F, Gasparini P, Fadda P, Alder H, Volinia S, Filippini A, Ziparo E, Riccioli A, Croce CM. Toll-like receptor 3 (TLR3) activation induces microRNA-dependent reexpression of functional RARβ and tumor regression. Proc Natl Acad Sci U S A. 2013 PMCID: PMC3683754.

34) Acunzo M*, Romano G*, Palmieri D, Laganá A, Garofalo M, Balatti V, Drusco A, Chiariello M, Nana-Sinkam P, Croce CM. Cross-talk between MET and EGFR in non-small cell lung cancer involves miR-27a and Sprouty2. Proc Natl Acad Sci U S A. 2013 PMCID: PMC3666747.
*These authors have contributed equally to this work
35) Romano G, Acunzo M, Garofalo M, Di Leva G, Cascione L, Zanca C, Bolon B, Condorelli G, Croce CM. MiR-494 is regulated by ERK1/2 and modulates TRAIL-induced apoptosis in non-small-cell lung cancer through BIM down-regulation. Proc Natl Acad Sci U S A. 2012 PMCID: PMC3478630.

36) Acunzo M, Visone R, Romano G, Veronese A, Lovat F, Palmieri D, Bottoni A, Garofalo M, Gasparini P, Condorelli G, Chiariello M, Croce CM. miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221 and 222. Oncogene. 2012 PMCID: PMC3719419.

37) Visone R, Veronese A, Rassenti LZ, Balatti V, Pearl DK, Acunzo M, Volinia S, Taccioli C, Kipps TJ, Croce CM. miR-181b is a biomarker of disease progression in chronic lymphocytic leukemia. Blood. 2011 PMCID: PMC3175784.

38) Veronese A, Visone R, Consiglio J, Acunzo M, Lupini L, Kim T, Ferracin M, Lovat F, Miotto E, Balatti V, D'Abundo L, Gramantieri L, Bolondi L, Pekarsky Y, Perrotti D, Negrini M, Croce CM. Mutated beta-catenin evades a microRNA-dependent regulatory loop. Proc Natl Acad Sci U S A. 2011 PMCID: PMC3064338.

39) Garofalo M, Di Leva G, Romano G, Nuovo G, Suh SS, Ngankeu A, Taccioli C, Pichiorri F, Alder H, Secchiero P, Gasparini P, Gonelli A, Costinean S, Acunzo M, Condorelli G, Croce CM. miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell. 2009 PMCID: PMC2796583.

40) Taccioli C, Fabbri E, Visone R, Volinia S, Calin GA, Fong LY, Gambari R, Bottoni A, Acunzo M, Hagan J, Iorio MV, Piovan C, Romano G, Croce CM. UCbase & miRfunc: a database of ultraconserved sequences and microRNA function. Nucleic Acids Res. 2009 Jan PMCID: PMC2686429.

41) Zanca C, Garofalo M, Quintavalle C, Romano G, Acunzo M, Ragno P, Montuori N, Incoronato M, Tornillo L, Baumhoer D, Briguori C, Terracciano L, Condorelli G. PED is overexpressed and mediates TRAIL resistance in human non-small cell lung cancer. J Cell Mol Med. 2008 Dec PMCID: PMC4514119.

42) Iavarone C*, Acunzo M*, Carlomagno F, Catania A, Melillo RM, Carlomagno SM, Santoro M, Chiariello M. Activation of the Erk8 mitogen-activated protein (MAP) kinase by RET/PTC3, a constitutively active form of the RET proto-oncogene. J Biol Chem. 2006 Apr PMID: 16484222.
*These authors have contributed equally to this work

43) Iavarone C, Catania A, Marinissen MJ, Visconti R, Acunzo M, Tarantino C, Carlomagno MS, Bruni CB, Gutkind JS, Chiariello M. The platelet-derived growth factor controls c-myc expression through a JNK- and AP-1-dependent signaling pathway. J Biol Chem. 2003 Dec PMID: 14523011.

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