BIOGRAPHICAL SKETCH. NAME Mariella De Biasi. POSITION TITLE Associate Professor. era COMMONS USER NAME DEBIASI

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1 NAME Mariella De Biasi era COMMONS USER NAME DEBIASI BIOGRAPHICAL SKETCH POSITION TITLE Associate Professor EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION DEGREE YEAR(s) FIELD OF STUDY University of Padova B.S Medicinal Chemistry University of Padova Ph.D Pharmacology &Toxicology A. Personal Statement As an undergraduate and graduate student, I trained in systems physiology and in vivo behavioral analyses of rodent models. As a postdoc, I trained in ion channel biophysics and molecular biology with Arthur M. Brown. After becoming an independent investigator, I focused my studies on the nicotinic cholinergic system and its roles in normal brain function and drug addiction. During the past 16 years I made significant contributions to the nicotinic field by characterizing a number of nicotinic receptor mutant mice. My laboratory unveiled the role of various nicotinic acetylcholine receptor (nachr) subtypes in autonomic function, the mechanisms of anxiety, and the brain circuits underlying nicotine withdrawal. The main focus has been the analysis of mice null for the α3, α5, and β4 nachr subunits. Our studies have indicated a prominent role for those subunits in the behavioral effects of both low and high nicotine doses as well as their specific influence on the physical manifestations of nicotine withdrawal. Indeed, we were the first to show that expression of α5-, α2- and/or β4-containing nachrs in the medial habenula (MHb)/interpeduncular nucleus (IPN) axis is necessary for the manifestation of nicotine withdrawal. The MHb/IPN axis is also involved in anxiety, depression, seizure, and has a role in controlling the amounts of nicotine that animals self-administer. My lab has either generated or acquired a number of viral vectors that we are using to change nachr expression levels in the whole brain as well as in specific neuronal subtypes. Viral vectors for nachr subunit knockdown are also available that can be used to significantly reduce nachrs in the whole brain or specific neuronal populations. All these tools are supporting current, in depth analyses of nicotinic cholinergic mechanisms in nicotine and ethanol addiction, and will be used in the proposed studies on the mechanisms of morphine withdrawal. I have a track record of collaborative work with a number of colleagues in the nicotinic field and look forward to the interactions with Imad Damaj, already a collaborator, and Paul Kenny. Each of us brings to the table different kinds of expertise and approaches that are synergistic. In summary, I have demonstrated that I can direct and manage successful and productive research projects. The expertise acquired in the nicotinic cholinergic field, the techniques available to the lab, and my experience as mentor and lab director will allow me to successfully contribute to the proposed work. POSITIONS: Research Associate with Dr Arthur M. Brown Dept. Physiology and Biophysics, Baylor Coll. of Medicine Lecturer to Medical, Medicinal Chemistry and Pharmacy students University of Padua, Italy 1993 Postdoctoral Fellow with Dr. Arthur M. Brown Dept. Physiology and Biophysics, Baylor Coll. of Medicine 1994 Research Assistant Professor Assistant Professor, non-tenure track Assistant Professor, tenure track Assistant Professor, tenure track Division of Neuroscience, Baylor Coll. of Medicine Associate Professor, tenured Department of Neuroscience, Baylor Coll. of Medicine Assoc. Prof., Graduate Program in Translational Biology & Molecular Medicine, BCM (2ndary) Assistant Director, Center on Addiction, Learning, Memory, Dept Neuroscience, BCM

2 2013-present Associate Professor with tenure, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia present Director, Program on Cholinergic Mechanisms in Addiction and Metal Illness AWARDS and HONORS: 1981 Presidential Award for best composition on European Community: Future and perspectives High School Valedictorian 1987 B.S. in Medicinal Chemistry, summa cum laude 1994 Ph.D. thesis ranked first for the Doctorate in Pharmacology and Toxicology for the year Curtis Hankamer Basic Research Award for Junior Faculty Lyndon B. Johnson Award for most outstanding research project. The Am. Heart Assoc. -TX Affiliate Distinguished lecture, American Society for Peripheral Nerve, Los Angeles, June 19-21, The Whitaker Foundation for Biomedical Engineering Award Barbara and Corbin J. Robertson, Jr. Presidential Award for Excellence in Education Selected National Scientific Participation and Editorial Boards: 2001 Reviewer: NIDA Special Emphasis Panel Reviewer: American Heart Association, Western Review Consortium, Committee 2b Reviewer: Tobacco-Related Disease Research Program (TRDRP) 2006-present Reviewer: Alzheimer s Association 2006 Reviewer: ad hoc reviewer for the National Science Foundation (NSF) 2006-present Editorial Board of Tabaccologia, member 2008 Reviewer: NIH Diversity Predoctoral Fellowship Study Section {ZRG1-HOP-Z (29)} 2010 Reviewer: Israel Science Foundation 2011 Reviewer: ad hoc for NIH-MNPS 2011 Reviewer: ad hoc reviewer for NIH ZRG1-MDCN-T(04), 2011 Reviewer: ad hoc reviewer for NIH ZRG1-MDCN-A 2011 Reviewer: ad hoc reviewer for NIH-CEBRA 2011 Reviewer for Alzheimer's and Related Diseases Research Award Fund (ARDRAF) 2011 Reviewer for the Biomedical Innovation in public-private Research Partnership program of the French National Research Agency 2011 Participant: Think Tank. The NCI Network on Biobehavioral Pathways in Cancer: Neural Mechanisms that Underlie Biobehavioral Pathways in Cancer. October Appointed member of NIH-MNPS study section SRNT (Society for Research on Nicotine and Tobacco)- Basic Science Co-Chair SFN (Society for Neuroscience) - Program Committee, member 2015 Reviewer, Reviewer, National Cancer Institute (NCI) Tobacco Control Monograph Series: A Socioecological Approach to Addressing Tobacco-Related Health Disparities. C. BIBLIOGRAPHY OF SELECTED RELEVANT PUBLICATIONS (from over 80 peer-reviewed publications): Most relevant to the present application 1. Salas, R., Pieri, F., De Biasi, M.: Decreased Signs of Nicotine Withdrawal in Mice Null for the Beta4 Nicotinic Acetylcholine Receptor Subunit. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 24(45): , *Evaluated by Faculty of 1000 Biology: 2. Salas, R., Main, A., Gangitano, D., De Biasi, M.: Decreased Withdrawal Symptoms but Normal Tolerance to Nicotine in Mice Null for the Alpha7 Nicotinic Acetylcholine Receptor Subunit. Neuropharmacology 53(7): , *Evaluated by Faculty of 1000 Medicine: 3. R. Salas, R. Sturm, J. Boulter, M. De Biasi. Nicotinic receptors in the habenulo-interpeduncular system are necessary for nicotine withdrawal in mice (2009). J. Neurosci. 29: *Evaluated by Faculty of 1000 Medicine ( 4. M. De Biasi & J.A. Dani (2011). Reward, Addiction, Withdrawal to Nicotine. Annu. Rev. Neurosci. 34: PMID:

3 5. Mineur YS, Abizaid A, Rao Y, Salas R, DiLeone RJ, Gundisch D, Diano S, De Biasi M, Horvath TL, Gao XB, Picciotto MR. (2011). Nicotine decreases food intake through activation of POMC neurons. Science. 332: PMID: Muldoon P.P., Jackson K.J., Perez E., Harenza J.L., Rais B., Anwar H.,Zaveri N.T., Maskos U., McIntosh J.M., Miles M.F., Chen X., Maldonado R., De Biasi M., Damaj M.I.: The alpha3beta4* nicotinic acetylcholine receptor subtype mediates physical dependence to morphine: Human and mouse studies (2014). The British Journal of Pharmacology 171(16): PMID: Harenza J.L., Muldoon P., De Biasi M., Miles M.F., Damaj M.I.: Genetic variation within the Chrna7 gene modulates nicotine reward-like phenotypes in mice (2014) Genes Brain & Behavior Nov 29. doi: /gbb [Epub ahead of print]. PMID: Dao D.Q., Perez E.E., Teng Y., Dani J.A., & De Biasi M.: Nicotine Enhances Excitability of Medial Habenular Neurons via Facilitation of Neurokinin Signaling (2014). The Journal of Neuroscience 34(12): PMID: Jackson KJ, Muldoon PP, De Biasi M, Damaj MI. New mechanisms and perspectives in nicotine withdrawal. Neuropharmacology.(2014) Nov 26. pii: S (14) doi: /j.neuropharm [Epub ahead of print] Review. PMID: Muldoon, P.P., Jackson, K.J., Perez, E., Harenza, J.L., Molas, S,, Rais, B., Anwar. H., Zaveri, N.T., Maldonado, R., Maskos, U., McIntosh, J.M., Dierssen, M., Miles, M.F., Chen, X., De Biasi, M., Damaj, M.I.: The α3β4* nicotinic ACh receptor subtype mediates physical dependence to morphine: mouse and human studies. British Journal of Pharmacology. (2014) Aug;171(16): doi: /bph PMID: Acevedo-Rodriguez A, Zhang L, Zhou F, Gong S, Gu H, De Biasi M, Zhou FM, Dani JA. Cocaine inhibition of nicotinic acetylcholine receptors influences dopamine release. Front Synaptic Neurosci. (2014) Sep 4;6:19. doi: /fnsyn ecollection PMID: Perez E, Quijano-Cardé N, De Biasi M. Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine. Neuropsychopharmacology (2015) Mar 19. doi: /npp [Epub ahead of print]. PMID: Additional relevant publications: 1. Salas, R., Baldwin, P., De Biasi, M., Montague, P.R.: Bold Responses to Negative Reward Prediction Errors in Human Habenula. Frontiers in Human Neuroscience 4(article 36): 1-7, R. Salas, B. Fung, R. Sturm, M. De Biasi (2012). Abnormal Social Behavior in Nicotinic Acetylcholine Receptor Beta 4 Subunit Null Mice. Nicotine and Tobacco Research 15(5): , PMID: Freedman ML, Monteiro AN, Gayther SA, Coetzee GA, Risch A, Plass C, Casey G, De Biasi M, Carlson C, Duggan D, James M, Liu P, Tichelaar JW, Vikis HG, You M, Mills IG (2011). Principles for the post-gwas functional characterization of cancer risk loci. Nature Genetics 43: PMID: Morel C., Fattore L., Pons S., Marti F., De Biasi M., Lathrop M., Fratta W., Maskos U. and Faure P.: Native and polymorphic α5* nicotinic receptors in the ventral tegmental area regulate nicotine intake (2014). Molecular Psychiatry 19(8): PMID: (press release: 5. Acevedo-Rodriguez, A., Lifen Zhang, L., Zhou, F., Gong, S., Gu, H., Doux, M.S., De Biasi, M., Fu-Ming Zhou, F-M., Dani, J.A.: Cocaine Inhibition of Nicotinic Acetylcholine Receptors Influences Dopamine Release.Frontiers in Synaptic Neuroscience Sep 4;6:19. doi: /fnsyn ; PMID: D. ONGOING RESEARCH PROJECTS : 1. Title: Transdisciplinary Research in Cancer of the Lung (TRICL) NIH/NCI U19CA /01/10-06/28/15 Amos PI of the Consortium Grant, De Biasi PI of one of the projects in Area 2 Goals: The goal of the projects in Area 2 is to conduct functional studies of nicotinic candidate lung cancer susceptibility genes that are discovered by human genetic studies

4 2. Title: Alpha 5 nachr is a Risk Factor within the Dopamine System for Nicotine NIH-NIDA R01 DA /01/14 04/30/19 Dani PI; De Biasi co-pi) Goals: We will investigate α5 s mechanistic action on the midbrain dopamine (DA) systems that reinforce rewarding and addictive behaviors. 4. Title: Influence of flavor additives on e-cigarette consumption during adolescence. TCORS /FDA/ UPenn Tobacco Center of Regulatory Science 10/01/14 09/30/15 De Biasi (PI) Goals: Study how flavor additives in e-cigarettes enhance nicotine reward and reinforcement by establishing an e-cigarette vapor delivery system in preclinical models of nicotine dependence during adolescence. RESEARCH PROJECTS COMPLETED DURING THE LAST FIVE YEARS: 1. Title: Cholinergic modulation of anxiety-related brain circuits Penn Medicine Neuroscience Center 02/01/14 01/31/15 De Biasi (PI) 2. Goals: Demonstrate a role for the MHb-IPN axis in anxiety-related behavior, and collect feasibility data on in vivo real-time measurement of neurotransmitter levels.title: Genomic, Neural, Preclinical Analysis for Smoking Cessation Diana Helis Henry Medical Research Foundation; No Grant Number Given. 04/01/11-03/31/14 Dani PI; De Biasi co-i Goals: An interdisciplinary and translational program to explore the genetic and neuronal underpinnings of nicotine dependence. A patient base of 3000 patients enrolled in tobacco cessation clinical studies are used to identify new genomic targets that are associated with cigarette smoking. 3. Title: Genetic Influences Over Nicotine Withdrawal NIH-NIDA R21 DA /17/10-12/30/13 Goals: Study the effects of α5 nachr single nucleotide polymorphisms on the manifestations of nicotine withdrawal. 4. Title: Stress, anxiety, and nicotine withdrawal NIH-NIDA RO1 DA /01/04-06/31/13 Goals: Study the interaction between stress and chronic administration of nicotine in nicotinic mutant mice. 5. Title: Effects from Nicotinic Receptor Variations on Smoking Behaviors and Lung Cancer Risk Cancer Prevention and Research Institute of Texas (CPRIT); RP /01/10-10/31/13 Amos PI, De Biasi co-i) Goals: Behavioral phenotyping of control and lung cancer patients carrying variants of nicotinic cholinergic receptor genes. 6. Title: Creation and Characterization of Animal Models of Nicotinic Receptor Cancer Risk Factors Cancer Prevention and Research Institute of Texas (CPRIT) RP /01/10-10/31/13 Dani PI, De Biasi co-i Goals: Create mouse lines expressing WT and D398N α5 nachrs in the VTA to study the impact of the α5 SNP on the electrophysiological properties of dopaminergic neurons. 7. Title: Regulation of Proteasomal function by nicotine NIH-NIDA R21 DA /03/08-01/31/10 De Biasi P.I Goals: Study the effects of nicotine of the function of the proteasome 8. Title: Nicotinic-purinergic modulation of bladder contraction NIH-NIDDK R01 DK /01/05-02/28/10 Somogyi P.I., De Biasi Co-I. Goals: Study the interaction of cholinergic and purinergic mechanisms in the bladder 9. Title: Chromosome 15, lung cancer risk, and proteasomal gene variants. NCI P30 Pilot Project Award 07/01/09-06/30/10

5 Goals: Generate lymphoblastoid cell lines from control and lung cancer patients carrying SNP in the PSMA4 gene to determine how non-synonymous SNPs affect proteasomal activity.