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Laure Aurelian, PhD

Academic Title:

Professor Emeritus

Primary Appointment:

Pharmacology

Location:

MSTF 500F

Phone (Primary):

(410) 706-3895

Education and Training

Tel-Aviv University, Tel-Aviv, Israel
MS Microbiology, 1962.

Johns Hopkins University, Baltimore, MD
Ph.D. Virology, 1966

Johns Hopkins University, Baltimore, MD
Postdoctoral fellowship in Virology, 1966-1967

Biosketch

I am the first woman to receive a PhD degree from the Johns Hopkins School of Medicine. I received my first R01 award in 1970 and have since been continuously supported by NIH grants.  I am the author of 310 publications in outstanding peer-reviewed journals and numerous review articles and book chapters and I am the inventor of 14 US and foreign patents. I trained over 60 postdoctoral and 37 predoctoral fellows, virtually all of whom hold Academic Positions.

Over the last 35-40 years my laboratory has made major significant contributions to science. One of these has been the development of a better understanding of the molecular and cellular factors that define infection with Herpes simplex virus type 2 (HSV-2) and the role that it plays in human disease. Another major contribution has been the elucidation of factors involved in disease development and the demonstration that inhibitory (Tregs and Th2) cell pathways are involved in the causation of recurrent disease. These efforts culminated in the development of a therapeutic HSV vaccine that has successfully completed phase I/II clinical studies. A third significant contribution has been the definition of viral genes in disease development. We showed that a HSV-2 gene regulates cell proliferation, unregulated cellular replication and neoplastic transformation, associated with human cancer and a viral gene is involved in the control of neuronal cell life/death decisions. We established the mechanism whereby this viral gene inhibits neuronal cell death and documented its evolutionary relationship to the cellular small heat shock protein H11 (HspB8), which we were the first to identify and clone and show that it has tumor suppressor activity. Another significant contribution to science made by our laboratory is in the understanding of recurrent erythematous skin lesions, known as erythema multiforme. We showed that these lesions are caused by non-permissive HSV infection of circulating CD34+ stem cells and the resulting induction of stem cell differentiation into antigen-presenting dendritic cells that target the skin.

The most recent significant contribution to science made by our laboratory is in oncolytic virotherapy, an emerging cancer therapeutic approach with relatively modest clinical efficacy. We developed an oncolytic virus (OV), known as DPK, with potent oncolytic activity in melanoma due to its multimodal activity. ∆PK lyses cancer stem cells (CSCs), activates numerous program cell death pathways and reverses the immunosuppressive tumor microenvironment responsible for therapeutic resistance. Specifically, ∆PK decreases tumor cell secretion of immunosuppressive and pro-cancerous cytokines (viz. IL-10 and IL-18) while concomitantly increasing secretion of pro-inflammatory cytokines (TNF-α, GM-CSF, IL-6 and IL-1β). It upregulates the NKG2D ligand, MICA expressed by cytotoxic NK and T cells, and downregulates the negative immune checkpoint regulator cytotoxic T-lymphocyte antigen-4 (CTLA-4). The virus is well tolerated in human patients in whom it also alters the T cell balance in favor of immunostimulatory responses.

Highlighted Publications

Aurelian, L., and Wagner, R.R. Two populations of herpesvirus virions which appear to differ in physical properties and DNA composition. Proc. Natl. Acad. Sci. U.S.A. 56:902-909, 1966.

Aurelian, L., Schumann, B., Marcus, R.L., and Davis, H.J.  Antibody to HSV-2 induced tumor-specific antigens in sera from patients with cervical carcinoma.  Science 181:161-164, 1973.

Aurelian, L.  Persistence and expression of the HSV-2 genome in cervical tumor cells. Cancer Res. 34:1126-1135, 1974.

Jariwalla, R.J., Aurelian, L., and Ts'o, P.O.P.  Tumorigenic transformation induced by a specific fragment of herpes simplex virus type 2 DNA.  Proc. Natl. Acad. Sci. 77:2279-2283, 1980.

Jariwalla, R.J., Aurelian, L., and Ts'o, P.O.P.  Immortalization and neoplastic transformation of normal diploid cells by various DNA fragments of herpes simplex virus type 2.  Proc. Natl. Acad. Sci. 80:5902-5906, 1983.

Hayashi, Y., Iwasaka, T., Smith, C.C., Aurelian, L., Lewis, G.K., and Ts'o, P.O.P. Multistep transformation by defined fragments of herpes simplex virus type 2 DNA:  Oncogenic region and its gene product.  Proc. Natl. Acad. Sci. 82:8493-8497, 1985.

Smith, C.C., Aurelian, L., Reddy, M.P., Miller, P.S., and Ts'o, P.O.P.  Antiviral effect of an oligonucleoside methylphosphonates complementary to the splice junction of herpes simplex virus type 1 immediate early pre-mRNA 4 and 5. Proc. Natl. Acad. Sci. 83:2787-2791, 1986.

Yasumoto, S., Hayashi, Y., Aurelian, L.  Immunity to herpes simplex virus type 2:  Suppression of virus-induced immune responses in ultraviolet B irradiated mice.  J. Immunol. 139:2788-2793, 1987.

Wachsman, M., Aurelian, L., Smith, C.C., Perkus, M.E., and Paoletti, E.  Regulation of expression of herpes simplex virus (HSV) glycoprotein D in vaccinia recombinants affects their ability to protect from cutaneous HSV-2 disease.  J. Inf. Dis. 159:625-634, 1989.

Kulka, M., Smith, C.C., Aurelian, L., Fishelevich, R., Blake, K., Miller, P. and Ts'o, P.O.P.  Site specificity of the inhibitory effects of oligonucleotide methylphosphonates complementary to the acceptor splice junction of HSV-1 pre-mRNA 4.  Proc. Natl. Acad. Sci. 86:6868-6872, 1989.

Imafuku, S., Kokuba, H., Aurelian, L., Burnett, J.  Expression of herpes simplex virus DNA fragments located in epidermal keratinocytes and germinative cells is associated with the development of erythema multiforme lesions.  J. Invest. Dermatol. 109:550-556, 1997.

Perkins D., Pereira E.F.R., and Aurelian L. The HSV-2 R1 PK (ICP10 PK) functions as a dominant regulator of apoptosis in hippocampal neurons by activating the ERK survival pathway and upregulating the anti-apoptotic protein Bag-1. J. Virol. 77:1292-1305, 2003.

Gober, M., Smith, C.C., Ueda, K., Toretsky, J., and  Aurelian, L. Forced expression of the H11 heat shock protein can be regulated by DNA methylation and trigger apoptosis in human cells. J Biol Chem. 278:37600-37609, 2003.

Ono F, Sharma B.K., Smith C.C., Burnett J.W., Aurelian L. CD34+ cells in the peripheral blood transport herpes simplex virus DNA fragments to the skin of patients with erythema multiforme (HAEM). J Invest Dermatol. 124:1215-24, 2005.

Laing, J.M., Gober, M.D., Golembewski, E.K., Thompson, S. M., Gyure, K.A., Yarowski, P.J. and Aurelian, L. Intranasal administration of the growth compromised HSV-2 vector DRR prevents kainate induced seizures and neuronal loss in rats and mice. Mol Therapy. 13:870-881, 2006.

Li, B., Smith, C.C., Laing, J.M., Gober, M.D., Liu, L., and Aurelian L. Forced expression of the heat shock protein H11 triggers growth arrest and apoptosis of melanoma cells through activation of Transforming growth factor b activated kinase 1 (TAK1). Oncogene. 26:3521-3531, 2007.

Liu J., Yang A.R.S.T., Kelly T., Puche A.C., Esoga C., June H.L. Jr., Elnabawi A., Merchentaler I., Sieghart W.,  June H.L. Sr., Aurelian L. Binge alcohol drinking is associated with GABAA a2-regulated TLR4 expression in the central amygdala. Proc. Nat. Acad. Sci. USA 108:4465-70, 2011.

June H.L., Liu J., Warnock K.T., Bell K.A., Balan I., Bollino D., Puche A., Aurelian L. CRF-amplified neuronal TLR4/MCP-1 signaling regulates alcohol self-administration. Neuropsychopharmacology. 40:1549-59, 2015.

Aurelian L., Warnock K.T.,  BalanI., PucheA., June H.  TLR4 signaling in VTA dopaminergic neurons regulates impulsivity through tyrosine hydroxylase modulation Translational Psychiatry. e815; doi:10.1038/tp.2016.72, 2016.

Research Interests

My current studies focus on the role of genetics in alcoholism. Alcohol-dependence is a complex disorder that initiates with episodes of excessive alcohol drinking known as binge drinking and has a 50-60% risk contribution from inherited susceptibility genes. Cognitive impulsivity is a heritable trait that may set the stage for transition to alcohol dependence but its role in the ethanol-seeking behavior and the involved genes are still poorly understood. We developed novel technologies designed to address these limitations, including the generation of non-replicating HSV-based siRNA vectors. We showed that the immunomodulatory gene Toll-like receptor 4 (TLR4) is over-expressed in neurons from binge-drinking alcohol-preferring P rats at brain sites that regulate both impulsivity and binge drinking. TLR4 is expressed by GABAergic or dopaminergic neurons at distinct brain sites. It is innately activated in the alcohol-preferring rats and regulates both impulsivity and the initiation of excessive alcohol drinking. Involved pathways include expression of the chemokine MCP-1, which also functions as a neurotransmitter that controls neuronal plasticity and excitability, and a cAMP-dependent protein kinase (PKA)/cyclic AMP response element binding protein (CREB) signal that regulates dopamine synthesis through tyrosine hydroxylase production. GABA, the GABAA receptor a2 subunit, the hormone corticotropin-releasing factor CRF and neuronally expressed IgG are involved in the regulation of the TLR4 signal. Ongoing studies are designed to further elucidate the mechanisms that regulate TLR4 activation as it relates to the initiation of excessive alcohol drinking and its transition to alcohol dependence. The mechanisms whereby innate immunity-related signaling control addiction through the regulation of plasticity and excitability are also under investigation.

Awards and Affiliations

Academic Appointments

  • Professor, Pharmacology
  • Professor, Microbiology and Immunology
  • Member, Greenebaum Cancer Center
  • Founder Member, Center for Stem Cell Biology and Regenerative Medicine
  • Member Neuroscience Program

 Professional Service (Selected)

  • Member NCI, NIAID site visit teams
  • Member Epidemiology and Immunology Study Section, NCI
  • Member Special Virus Cancer Program, NCI
  • Member, B.W. Wood Foundation Student Research Committee,
  • President, American Association of University Professors, JHU
  • Member, Program of Scientific Affairs, Organization of American States
  • Membership Committee, American Venereal Disease Association
  • Member, USA-USSR Workshop on the Epidemiology of Gynecologic Cancer
  • Member, Genital Herpes Panel, American College of Obstetrics and Gynecology
  • Member, Mid-Atlantic East Coast Herpesvirus Association
  • Organizing Committee, Women in Science Symposium, Kennedy Institute
  • Member, NIH Consensus Conference on Cervical Cancer Screening
  • Member, Cancer Research Manpower Review Committee, NIH
  • Member, Symposium on Sexually Transmitted Disease
  • Member, Scientific Committee UNESCO International Biomedical Institute
  • Member, Organizing Committee, ASM Seminars Virus Immunosuppression
  • Member, AACR Committee for Membership Development
  • Member, Review Committee NIH Fogarty International Research Collaboration
  • Member, Review Committee NIH Hitchings-Elion Fellowships
  • Member, Organizing Committee IUVDT European Congress on STDs
  • Member General Medicine A Study Section, NIH
  • Member, Advisory Committee, European Research Organization on Genital Infection and Neoplasia

Honors Awards and International activity (Selected)

  • Distinguished Young Scientist Award, Maryland Academy of Science (1970)
  • Visiting Lecturer, Osaka University School of Medicine, Japan (1977)
  • Member, Delegation for Cancer Epidemiology, US-USSR Joint Committee on Health Cooperation (1979)
  • Keynote Address, International Congress of Viral Oncology, Beaumont-Bonelli Foundation for Cancer Research, Italy (1979)
  • Honorary Member D.A. Boyes Society of Gynaecologic Oncology, British Columbia, Canada (1983)
  • The World Who's Who of Women in Education (1983)
  • Who's Who in American Women (1983)
  • Keynote Address, Japanese Society of Clinical Virology Annual Meeting (1984)
  • Personalities of America Distinguished Service to the Medical Profession (1985)
  • Visiting Professor, University of Bologna, Bologna, Italy (1986)
  • Honorary Professor, University of Catania, Italy (1988)
  • Keynote Address, 900th Anniversary, University of Bologna (1987)
  • Honorary Lecture, Epidemiology, Virology Symposium, Taiwan (1988)
  • Guest Lecture, Indian Council of Medical Research (1988)
  • Honorary Medal Distinguished Contribution to Gynecologic Oncology Italy (1988)
  • Keynote Address, Universita Cattolica Del Sacro Cuore, Rome, Italy (1988)
  • Keynote Address, WHO Symposium on Sexually Transmitted Diseases, Cannes, France (1989)
  • Honorary Lecture, International Symposium on the Pathogenesis and Control of Viral Infections, Beijing, China (1989)
  • Keynote Address, 7th World Congress of Cervical Pathology and Colposcopy, Rome, Italy (1990)
  • K. Vephvadze Memorial Award; Georgian Society of Oncologists, Republic of Georgia (1990)
  • Award, Premio XXIV Casali 90 ASS. Pro Loco Bronte Edizione Speciale Medicina, Catania, Italy (1990)
  • Opening Address, International Meeting of Gynaecological Oncology, Venice, Italy (1991)
  • Keynote Address, European Congress for Infectious Diseases in Obstetrics and Gynecology (1992)
  • Who's Who in the World (1995)
  • Honorary Lecture International Conference Anticancer Research Greece (1995)
  • President and Chair, EUROGIN conference, Paris France (1996)
  • Guest Lecture, Drug Development Inaugural Symposium, Brazil (1998).
  • Keynote Lecture, International Symposium Mol Medicine, Athens Greece (1999)
  • Outstanding Scientists of the 21st Century, Cambrige, England (2000)
  • Advisor, National Collegiate Inventors Competition (2001)
  • International personality of the Year, (2001)
  • Chair Progress in Molecular Medicine Symposium, Greece (2002).
  • Keynote address, Annual meeting Japanese Dermatological Association (2004)
  • Who’s Who in America (2006)
  • Keynote address, HSV International Meeting, Japan (2007)
  • Keynote address, Annual Meeting Japanese Dermatology Association (2009)
  • Visiting Professor, Chinese Academy of Medicine (2010)
  • Outstanding Contribution Award; World Congress of Dermatology, Seoul Korea (2011)
  • Honorary professor, Second Military Medical University, Shanghai, China (2012-2016)

Professional Activity

  • Member NCI, NIAID site visit teams
  • Member Epidemiology and Immunology Study Section, NCI
  • Member Special Virus Cancer Program, NCI
  • Member, B.W. Wood Foundation Student Research Committee,
  • President, American Association of University Professors, JHU
  • Member, Program of Scientific Affairs, Organization of American States
  • Membership Committee, American Venereal Disease Association
  • Member, USA-USSR Joint Committee on Health Cooperation
  • Member, Panel on Genital Herpes Panel, American College of ObGyn
  • Member, Mid-Atlantic East Coast Herpesvirus Association
  • Organizing Committee, Women in Science Symposium, Kennedy Institute
  • Member, NIH Consensus Conference on Cervical Cancer Screening
  • Member, Cancer Research Manpower Review Committee, NIH
  • Member, Symposium on Sexually Transmitted Disease
  • Member, Scientific Committee UNESCO International Biomedical Institute
  • Member, American Society Microbiology Seminar Organizing Committee
  • Member, AACR Committee for Membership Development
  • Member, Review Committee NIH Fogarty International Research Collaboration
  • Member, Review Committee NIH Hitchings-Elion Fellowships
  • Member, Organizing Committee IUVDT European Congress on STDs
  • Member General Medicine A Study Section, NIH
  • Member, Advisory Committee, European Research Organization on Genital Infection and Neoplasia