OMB No. 0925-0001 and 0925-0002 (Rev. 03/2020 Approved Through 02/28/2023)
Provide the following information for the Senior/key personnel and other significant contributors.
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NAME: Miele, Lucio
eRA COMMONS USER NAME (credential, e.g., agency login): lmiele
POSITION TITLE: Professor and Department Head, Department of Genetics, Assistant Dean for Translational Science, Director for Inter-Institutional Programs, Stanley Scott Cancer Center, LSU Health Sciences Center-New Orleans.
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION DEGREE
FIELD OF STUDY
University of Naples, Italy
University of Naples, Italy
University of Naples, Italy/Max-Planck Institute for Molecular Genetics, Berlin, Germany
Postdoctoral fellowship 03/82
Board certification in Italy
ECFMG, Bethesda, MD 05/97 ECFMG certification
A. Personal Statement
Dr. Miele is the Head of the 17-faculty Genetics Department at LSUHSC. He oversees the newly created Precision Medicine Program and Bioinformatics and Genomics Research Program. He also serves in the following capacities: LA CaTS Center: Director of Biomedical Informatics; LSUHSC Stanley Scott Cancer Center, Director for Inter-Institutional Programs; UAB CCTS Partner Network: Co-Director; Mid-South OHDRC extension on Social Determinants of Health Disparities: LSUHSC PI. Dr. Miele completed his PhD work dissertation at the Max-Planck Institute for Molecular Genetics in Berlin and his fellowship at Human Genetics Branch (NICHD). He remained at NICHD for 8 years, working on progesterone-induced immune-modulatory secretoglobins. Upon joining CBER, FDA, he began his work on Notch in cancer and the immune system. Dr. Miele was a member of the Divisions of Monoclonal Antibodies and Clinical Trials Design and Analysis at and CBER, FDA and has served as co-chair of the NCI CTEP task force on clinical trials targeting cancer stem cells. A large part of Dr. Miele’s research is devoted to biomarker discovery for mechanism-based cancer therapeutic trials and investigations of cancer stem cell- and immunity-regulatory genes, such as Notch. His initial investigation of Notch targeting in breast cancer animal models was funded by a CDMRP IDEA grant in 2003. His lab first demonstrated that Notch1 is expressed in human breast cancer, that Notch is activated by endocrine therapy and causes endocrine resistance by activating ER-dependent transcription, that Notch4 also causes endocrine resistance and that Notch regulates cancer cell mitochondrial metabolism in triple-negative breast cancer. Along with Dr. Spyros Artavanis-Tsakonas, the scientist who isolated the Notch gene, he edited a Springer-Verlag volume on targeting Notch in cancer. He has advised academic and industry groups on therapeutic targeting of Notch in oncology. Dr. Miele is an experienced manager of large projects. At LSUHSC, Dr. Miele has taken the lead in precision medicine, creating the Precision Medicine Program and becoming the site PI for the Southern “All of Us” initiative, as well as receiving an NCI P20 grant in partnership with Moffitt Comprehensive Cancer Center to perform breast cancer health disparities precision medicine research and a SPORE P20 to investigate the immunogenomic diversity of human triple-negative breast cancers.
B. Positions and Honors
2015- Professor and Head, Department of Genetics, LSU Health Sciences Center
2014- Professor of Genetics and Director of Inter-institutional Programs, Stanley S. Scott Cancer Center, LSU Health Sciences Center New Orleans
2009-2014 Director, University of Mississippi Medical Center Cancer, Ergon Professor of Medicine and Pharmacology
2007-2009 Associate Director for Translational Science, Cardinal Bernardin Cancer Center, Loyola
2005 Professor (tenure) of Pathology and Pharmacology, Director, Breast Cancer Research Program, Cardinal Bernardin Cancer Center, Loyola University Chicago
2001-2005 Associate Professor (tenured) of Biopharmaceutical Sciences, University of Illinois at Chicago; Director, Molecular Pathogenesis and Signaling Program, UIC Cancer Center
1998-2001 Assistant Professor, Department of Pathology, Cardinal Bernardin Cancer Center, Loyola University Chicago Medical Center, Maywood, IL; Chair, Admission committee to the Graduate Program in Molecular Biology; Director, DNA Sequencing and Recombinant DNA Laboratory, and Proteomics Laboratory, Molecular Pathology Research Facility, Department of Pathology
1997-1998 Acting Chief, Laboratory of Cell Biology, Division of Monoclonal Antibodies, CBER, FDA; Chairperson, CBER scientists
1994-1997 Tenure-track Principal Investigator, Laboratory of Cell Biology, Division of Monoclonal Antibodies, CBER, FDA
1994-1998 Member, Division of Clinical Trials Design and Analysis, CBER/FDA NIH1986-1988 Visiting Fellow, Human Genetics Branch, Section on Developmental Genetics, NICHD, NIH
1990-1994 Visiting Associate, Section on Developmental Genetics, Human Genetics Branch, NICHD,
1989-1990 Adjunct Scientist, Section on Developmental Genetics, Human Genetics Branch, NICHD, NIH
1984-1986 Graduate student, Max-Planck Institut fuer Molekulare Genetik, Berlin FRG, where he completed his Ph.D. dissertation work on plasmid RP4 DNA primase genes and contiguous genes, including the kanamycin-resistance gene. Co-advisor was Dr. Erich Lanka (Abteilung Schuster)
1982-1983 During his residency, he also served as instructor, Institute of Biological Chemistry, First Faculty of Medicine and Surgery, University of Naples. Taught Biochemistry lab for medical students
Other Experience, Professional Memberships, Administrative and Scientific Institutional Leadership Positions:
2020- Assistant Dean for Translational Science, LSU Health Sciences Center New Orleans
2015- Director, Biomedical Informatics Key Component, LACATS Consortium
2014- Director of Inter-Institutional Programs, Stanley S. Scott Cancer Center, LSU. Coordinates collaborative translational and clinical research programs with other members of the Louisiana Cancer Research Consortium and with other regional academic institutions2015-pres. Co-Director, UAB-led Center for Clinical and Translational Sciences (CCTS; R. Kimberly, Director)
2009-2014 Director, University of Mississippi Medical Center Cancer Institute. Oversaw basic, translational and clinical cancer research, cancer clinical programs and cancer outreach and education at the University of Mississippi Medical Center
2008-2009 Associate Director for Translational Sciences, Cardinal Bernardin Cancer
2005-2009 Director, Breast Cancer Research Program, Cardinal Bernardin Cancer Center
2003-2005 Director, Molecular Pathogenesis and Signaling Program, UIC Cancer Center
Member: AACR, ASCO
J. Cancer Treatment and Metastasis (Editor in Chief), Oncogene, PlosOne, Molecular Cancer, Oncotarget, Frontiers in Molecular Medicine, Frontiers in Oncology (Associate Editor); J. Cell. Biochem. (Associate Editor), J. Exp. Clin. Canc. Res. (Executive Editor for the Americas), Curr. Mol. Med. (Associate Editor), Am. J. Cancer Res. Referee service for: Nature Cell Biology, Nature Communications, Cancer Cell, Science, Science Translational Science, P.N.A.S., Oncogene, Cancer Res., J. Clin Invest., In. J. Cancer, Biochemical J., Gastroenterology, Biochemistry, J. Immunol., European Journal of Biochemistry, European Journal of Cell Biology, Exp. Cell Res., Blood, PLoS Medicine, J. Leukocyte Biol., Gene, Leukemia, Cell Death and Differentiation, J. Cell Physiol., Mol. Cancer Ther., Cell and Tissue Res., Future Med., Mol. Medicine Book Series (Humana Press), Arch. Pathol. Lab Med., DNA and Cell Biol., Curr. Molecular Med., Clin. Cancer Res., Br. J. Cancer, J. Biol. Chem., Int. J. Cancer, Stem Cells and Development, Biotechnology, The Histochemical Journal, Clin. Diagn. Lab Immunol., Amino Acids, Prostaglandins.
Grant Proposal Review Service: The Wellcome Trust Fund, NIH (ET-1, DMP, BMCT NCI Study Sections, NCI P01 U54, P20 and SPORE Study Sections), NCRR/NCATS (CTSA), DOD, VA, ALW (The Netherlands), NSERC (Canada), AIRC (Italy), Cancer Research UK.
Public Health Responsibilities at FDA:
1994-1998 Had clinical review responsibilities for trials of biotechnology products, predominantly in the area of immunomodulatory agents.
1994-1998 Had review and supervisory responsibilities in the review of novel monoclonal antibodies to tumor antigens and viral antigens for diagnostic and therapeutic use.
1994-1998 Member of policy groups drafting other guideline documents pertaining to biotechnology drugs, including ICH (International Conference on Harmonization) guidelines.
1995-1997 Chairperson, Re-writing of the current Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use, issued in the U.S. Fed. Register 62 FR vol 40, 2/28/97, http://www.fda.gov/cber/points.htm
2021 Featured Speaker, NCI Webinar on the Intersection of Obesity and Cancer Health Disparities
2020 Featured Keynote Speaker, Case Western Reserve Cancer Center Conference on Cancer Health Disparities
2018 Session Chair, Gordon Research Conference on Notch, Bates College, ME
2017-2019 Scientific Organizer, “Notch Targeting in Cancer” conference, Cyprus
2016- Adjunct Professor of Medicine/Oncology, Tulane University Medical School
2015- Scientific Organizer, European CME course, Salerno Medical School, Italy
2012 International Research Award: Schola Medica Salernitana (Italy)
2012 Acharya P.C. Ray Gold Medal Award for Pioneering Research (India Science News Association)
2011 Organizer, 1st International Notch in Cancer Conference, Mykonos, Greece
2009 Symposium Chair, Early Clinical Trials Pipeline, International Conference on Drug Discovery Science and Technology, Shanghai, China
2009 Organizer, the Notch conference, Athens, Greece, October 2009
2008-2014 Member and co-Chair, NCI Task Force on Cancer Stem Cells
2008 Invited Speaker, the NCI Translates Conference (invitational only)
2007-2014 Adjunct Professor, Department of Biology, Temple University, Philadelphia
2007 Organizer, Invited Speaker: the Notch Conference, Athens, Greece
2007 Chair, Translational Symposium: The Notch Conference, Athens, Greece
2007- Adjunct Professor, Department of Biopharmaceutical Sciences, University of Illinois at Chicago
2006 Keynote Speaker, Italian Society of Neuroendocrinology, Florence and Milan, Italy
2005 Organizer and invited featured speaker, EMBO Workshop on Notch signaling in Development and Cancer, Rome, Italy
2001Honored by Illinois Lieutenant Governor for contributions to women’s cancer research
2000 Honored by Illinois Lieutenant Governor for contributions to women’s cancer research
1998 FDA/OTRR “On the spot” award for outstanding performance as an Acting Lab Chief and for contributions to FDA policy
1997 FDA Honor Award “for exceptional performance”, 1997
1983 Award for Outstanding Young Scientist, the Academy of Medical and Surgical Sciences, National Society of Sciences, Literature and Arts, Naples, Italy
1982 First in his M.D. class with highest GPA in the history of his Medical School
C. Contributions to Science (total publications 245 to date)
a. Elucidating crosstalk interactions between Notch signaling and other pathways relevant to breast cancer and hormone-dependent cancers. The Miele lab has been dissecting the interactions of Notch signaling with other major developmental pathways in the context of cancer biology and experimental therapy. Recent representative references include:
1. Hossain F, Sorrentino C, Ucar DA, Peng,Y, Matossian M, Wyczechowska D, Crabtree J, Zabaleta J
Morello S, Del Valle L, Burow M, Collins-Burow B, Pannuti A, Minter LM, Golde TE, Osborne BA, Miele L. Notch signaling regulates mitochondrial metabolism and NF-kB activity in triple-negative breast cancer cells via IKKα-dependent non-canonical pathways. 2018; Front. Oncol. doi.org/10.3389/fonc.2018.00575
2. Sabol RA, Bowles AC, Cote A, Wise R, O'Donnell B, Matossian MD, Hossain FM, Burks HE, Del Valle
3. Obesity-Altered Adipose Stem Cells Promote Radiation Resistance of Estrogen Receptor Positive Breast Cancer through Paracrine Signaling. Sabol RA, Villela VA, Denys A, Freeman BT, Hartono AB, Wise RM, Harrison MAA, Sandler MB, Hossain F, Miele L, Bunnell BA. Int J Mol Sci. 2020 Apr 15;21(8). pii: E2722. doi: 10.3390/ijms21082722. PMID: 32326381
4. Ran Y, Hossain F, Pannuti A, Lessard CB, Ladd GZ, Jung JI, Minter LM, Osborne BA, Miele L, Golde TE. gamma-Secretase inhibitors in cancer clinical trials are pharmacologically and functionally distinct. EMBO molecular medicine. 2017;9(7):950-66. PMID: 28539479; PMCID: PMC5494507.
b. Use of novel bio-informatics approaches to elucidate the integration between Notch signaling and other pathways in cancer precision medicine. In collaboration with bio-informatician Dr. Chindo Hicks, the Miele lab utilized novel methods correlating GWAS and gene expression profiling as well as driver prediction in cancer somatic exome data. Relevant references include:
1. Pannuti A, Filipovic A, Hicks C, Lefkowitz E, Ptacek T, Stebbing J, Miele L. Novel putative drivers revealed by targeted exome sequencing of advanced solid tumors.PLoS One. 2018 Mar 23;13(3):e0194790. doi: 10.1371/journal.pone.0194790. eCollection 2018. PMID: 29570743
2. Hicks C, Kumar R, Pannuti A, Backus K, Brown A, Monico J, Miele L. An Integrative Genomics Approach for Associating GWAS Information with Triple-Negative Breast Cancer. Cancer informatics. 2013;12:1-20. PMID: 23423317; PMCID: PMC3565545.
3. Hicks C, Koganti T, Brown AS, Monico J, Backus K, Miele L. Novel Integrative Genomics Approach for Associating GWAS Information with Intrinsic Subtypes of Breast Cancer. Cancer informatics. 2013;12:125-42. PMID: 23761956; PMCID: PMC3663490.
4. Hicks C, Kumar R, Pannuti A, Miele L. Integrative Analysis of Response to Tamoxifen Treatment in ER-Positive Breast Cancer Using GWAS Information and Transcription Profiling. Breast cancer: basic and clinical research. 2012;6:47-66. PMID: 22399860; PMCID: PMC3292850.
c. Discovery of the oncogenic role of Notch1 in solid tumors including breast cancer. The Miele lab showed that Notch1 is indispensable for transformation in this model downstream of Ras. Notch signaling has since been shown to be activated in a variety of human tumors carrying Ras mutations. Representative reference:
1. Weijzen S, Rizzo P, Braid M, Vaishnav R, Jonkheer SM, Zlobin A, Osborne BA, Gottipati S, Aster JC, Hahn WC, Rudolf M, Siziopikou K, Kast WM, Miele L. Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells. Nature medicine. 2002;8(9):979-86. PMID: 12185362.
2. Majumder S, Crabtree JS, Golde TE, Minter LM, Osborne BA, Miele L: Targeting Notch in oncology: the path forward. Nat Rev Drug Discov 2020 Dec 8. doi: 10.1038/s41573-020-00091-3. Online ahead of print. PMID: 33293690.
3. Means-Powell JA, Mayer IA, Ismail-Khan R, Sorrentino C, Majumder S, Miele L: A Phase Ib Dose Escalation Trial of RO4929097 (a γ-secretase inhibitor) in Combination with Exemestane in Patients with ER + Metastatic Breast Cancer (MBC) Clin. Breast Cancer 2022; 2:103-104
d. Contributions to health disparities research:
1. All of Us Research Program I, Denny JC, Rutter JL, Goldstein DB, Philippakis A, Smoller JW, Jenkins G, Dishman E: The "All of Us" Research Program. N Engl J Med 2019, 381:668-676.
2. Yedjou CG, Tchounwou PB, Payton M, Miele L, Fonseca DD, Lowe L, Alo RA. Assessing the Racial and Ethnic Disparities in Breast Cancer Mortality in the United States. International journal of environmental research and public health. 2017;14(5). PMID: 28475137; PMCID: PMC5451937.
3. Serrano-Gomez SJ, Sanabria-Salas MC, Hernandez-Suarez G, Garcia O, Silva C, Romero A, Mejia JC, Miele L, Fejerman L, Zabaleta J. High prevalence of luminal B breast cancer intrinsic subtype in Colombian women. Carcinogenesis. 2016;37(7):669-76. PMID: 27207651; PMCID: PMC4936382.
Link to full record of Dr. Miele’s publications: https://www.researchgate.net/profile/Lucio_Miele/publications
D. Additional Information: Research Support and/or Scholastic Performance: Active Research Support
NIH/NCATS, 1UL1TR003096-01 (Kimberly) 05/06/201 –04/30/2024 Role: Co-Director, site PI
Center for Clinical and Translational Sciences (CCTS)
Project Goals: The UAB CCTS will enhance human health by driving scientific discovery and dialogue across the bench, bedside, and community continuum. The CCTS Components support this overall mission in a highly integrative network of relationships.
NIH/NCI, P20CA202922-01A1 (Miele/Meade) 09/01/17 – 08/31/21 Role: MPI
The Southeast Partnership for Improving Research and Training in Cancer Health Disparities
Project Goals: The goal of the SPIRIT-CHD consortium is to execute 2 pilot research projects focused on cancer precision medicine in health disparities and train early stage investigators in biospecimen-based precision medicine research and community outreach.
NIH/NICHD, 2R01HD042280-01A1 (Fazleabas) 09/12/16 – 05/31/21 Role: Collaborator
Modulation of the Receptive Endometrium and Decidualization by Notch1
Project Goals: This application focuses on studying the role of Notch-1 in initiating the differentiation
of stromal fibroblasts into the decidual phenotype in response to Chorionic Gonadotropin and
NIH/NIGMS, 2U54GM104940-02 (Kirwan) 07/01/17 – 06/30/22 Role: KCA Leader
Louisiana Clinical and Translational Science Center
Project Goals: Louisiana is in the highest decile for mortality from chronic diseases. The LA CaTS Center will promote training and will facilitate and enhance clinical and translational research to accomplish the Center theme to address health disparities and improve health outcomes. Major areas of research focus will be obesity, diabetes, cardiovascular disease, cancer, aging and cognitive dysfunction.
NIH/NIGMS, 1P20GM121288-01 (Reiss) 08/15/17 – 05/31/22 Role: Mentor
Center for Translational Viral Oncology (CTVO)
Project Goals: The Center will advance basic and translational approaches to address virus-related cancers responsible for the disproportionate rate of these diseases in the State of Louisiana as compared with the rest of the nation.
NIH/NCI. P20 SPORE (A. Ochoa-Miele, MPIs) 09/19/18-08/31/21 Role: MPI, Project 1 PI
Understanding and Addressing Cancer Health Disparities in Louisiana
Project Goals: To establish research projects that bring together the best investigators and institutions in Louisiana conducting research on the genetics/genomics, immunology, and clinical and public health aspects of cancer with special emphasis on health disparities.
NIH/OD, 1OT2OD026548-01 (Korf) 07/01/18 – 06/30/23 Role: Consortium PI
Southern All of Us Network
Project Goals: The objective is to gather data from diverse population across United States to accelerate research and improve health. Researchers will use data from the program to learn more about how individual differences in lifestyle, environment, and biological makeup can influence health and disease.
PCORI/PCRF, REACHnet (Miele) 07/01/19 – 08/31/24 Role: Consortium PI
Research Action Network (REACHNet) clinical data repository
Project Goals: The goal of this project is to study clinical outcomes and factors contributing to morbidity and mortality for diseases affecting Louisiana patients.
Completed Recent Research Support:
NIH/NCI, P01CA166009-01A1 (Osborne) 09/20/16 – 08/31/19 Role: Project 1 PI
Targeting Multiple Diseases through Gamma Secretase
Cellestia Biotech CB-103 Study 12/01/2018 – 10/03/2019 Role: PI