Flavia Pichiorri, Ph.D., M.S.
- Leveraging Clinical Trials to Understand Resistance Therapies
- Understanding Multiple Myeloma Dissemination by Antibody-based Imaging
- Developing Novel CD38-therapeutic Interventions for Multi-relapsing Patients
- Immunopredictors in Mass Cytometry
- Leflunomide Therapy for Smoldering Multiple Myeloma and COVID-19
- Oncolytic Viruses as a Potential Therapy for Multiple Myeloma
- Generating Novel Therapeutic Treatments for Leukemia
- Development of Humanized Mouse Model
Flavia Pichiorri, Ph.D., M.S., is a professor in the Department of Hematologic Malignancies Translational Science.
Prior to joining City of Hope, Dr. Pichiorri was an assistant professor in the Division of Hematology atThe Ohio State University College of Medicine. Dr. Pichiorri graduated cum laude with her M.S. in molecular cell and development biology from the University of Rome “Tor Vergata.” She also received her doctorate in experimental medicine from the University of Rome “Tor Vergata” and completed her postdoctoral training at The Ohio State University in the Department of Molecular Virology, Immunology and Medical Genetics.
As a postdoctoral fellow and research scientist, Dr. Pichiorri demonstrated that microRNAs (miRNAs) are involved in the malignant transformation of plasma cells and that miRNA-dependent deregulation of critical genes contributes to multiple myeloma pathogenesis. She showed that recurrent molecular aberrations, such as p53 mutation/deletion, could affect the miRNA expression and therapeutic response of multiple myeloma cells, and that circulating miRNAs could be considered new prognostic biomarkers for multiple myeloma.
Continuing her work in experimental therapeutics at City of Hope, Dr. Pichiorri recently developed and demonstrated, and successfully completed a Phase 1 trial for an anti-CD38 antibody conjugate with a radiotracer to detect myeloma cell dissemination. She continues to develop and clinically test the anti-CD38 antibody conjugate with a therapeutic isotope for the imaging and treatment of myeloma. In addition to this work, Dr. Pichiorri is also the laboratory investigator of five active clinical trials.
Location
Education & Experience
2006, Ph.D., Experimental Medicine, University of Rome “Tor Vergata” Rome, Italy
1999, M.S., Molecular Cell and Development Biology, Cum Laude, University of Rome “Tor Vergata,” Rome, Italy
1996, B.S., Biological Science University of Rome “Tor Vergata,” Rome, Italy
2009, Postdoctoral Training, The Ohio State University, Columbus, OH
2021-present, Professor, Judy and Bernard Briskin Center for Multiple Myeloma Research, Department of Hematologic Malignancies Translational Science, City of Hope, Duarte, CA
2016-2021, Associate Professor, Judy and Bernard Briskin Center for Multiple Myeloma Research, Department of Hematologic Malignancies Translational Science, City of Hope, Duarte, CA
2011-2016, Assistant Professor, Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH
2010-2011, Research Scientist, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH, Laboratory of Carlo M Croce, M.D.
2006-2009, Postdoctoral Research, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH. Mentor: Carlo M Croce, M.D.
2004-2006, Visiting Ph.D. Student, Experimental Medicine Program, Department of Medical Genetics, Thomas Jefferson University, Philadelphia, PA. Mentor: Carlo M Croce, M.D.
2001-2004, Ph.D. Student, Experimental Medicine Program, Department of Internal Medicine, University of Rome “Tor Vergata,” Rome, Italy. Mentor: Luigi G Spagnoli, M.D.
1999-2001, Research Assistant, National Research Council, Institute of Neurobiology and Molecular Medicine, Rome, Italy. Mentor: Federico Cozzolino, M.D.
1997-1999, Research Student, School of Biological Science, University of Rome “Tor Vergata” Rome, Italy. Mentor: Mario Lo Bello, Ph.D.
Research
Laboratory
The Pichiorri lab is focused on basic and translational research in multiple myeloma.
Specifically, on:
(1) Preclinical and clinical experimental therapeutics in multiple myeloma
(2) Identification of genetic and epigenetic abnormalities involved in multiple myeloma pathogenesis
(3) Understanding the physiological role of multiple myeloma-derived extracellular vesicles in modulating the tumor microenvironment and their possible use as easily accessible biomarkers for multiple myeloma patient stratification at diagnosis and resistance to therapy.
Dr. Pichiorri has developed, patented and licensed novel approaches to diagnose and treat cancer both in Italy and in the U.S.
She has identified and characterized how miRNA deregulation in myeloma cells can be involved in drug response. Furthermore, she highlighted the role of epigenetic regulation in the clonal selection of plasma cells during disease progression. Dr. Pichiorri’s laboratory has shown that circulating miRNA in the serum of myeloma patients at diagnosis can be used as non-invasive biomarkers and that HDACi can affect the response to lenalidomide and oncolytic viruses through epigenetic modifications in vitro and in vivo.
She has proved that the process of downregulation of CD84 might serve as a novel therapeutic target in multiple myeloma to regulate T cell function by elevating T cell activity and hence reducing tumor burden.
Dr. Pichiorri’s lab was the first to provide the biological rationale of how targeting CD38 with therapeutic antibodies can synergize with proteosome inhibitor for myeloma treatment. Subsequently, Dr. Pichiorri’s lab developed novel CD38 conjugated antibodies for the imaging and treatment of myeloma. Dr. Pichiorri was also the first to suggest that resistance to anti-CD38 based therapies can be associated with changes in the tumor microenvironment more than in the cancer cells.
Currently, Dr. Pichiorri is developing 7 CD38-CD3 BIONICs to bring two cells closer together than with a classic T cell engager and has strong anti-cancer activity. The preclinical studies conducted in acute myeloid leukemia showed efficacy, and Dr. Pichiorri believes that BIONICs will also be a highly effective treatment in multiple myeloma.
Awards & Memberships
Memberships
2012, American Society of Hematology
2011, Multiple Myeloma Research Foundation, Roundtable, Member
2011, Research Grants Council of Hong Kong, Ad hoc Grant Reviewer
2010, Multiple Myeloma Research Consortium, Roundtable, Member
2004, American Association of Cancer Research
Publications
- Dona A, Caserta E, Singer M, Tandoh T, Nigam L, Winchester J, Chowdhury A, Zhu Y, Murtadha M, Pozhitkov A, Sanchez J, Vahed H, Coffey M, Marcucci G, Krishnan A, Nuovo G, Sborov D, Hofmeister C, Pichiorri F. Proteasome inhibition enhances myeloma oncolytic reovirus therapy by suppressing monocytic anti-viral immune responses. 2022/01; :2022.03.29.22272857. doi: 10.1101/2022.03.29.22272857.
- Adhikarla V, Awuah D, Brummer AB, Caserta E, Krishnan A, Pichiorri F, Minnix M, Shively JE, Wong JYC, Wang X, Rockne RC. A Mathematical Modeling Approach for Targeted Radionuclide and Chimeric Antigen Receptor T Cell Combination Therapy. Cancers (Basel). 2021 Oct 15;13(20). doi: 10.3390/cancers13205171. PubMed PMID: 34680320; PubMed Central PMCID: PMC8533817.
- Minnix M, Adhikarla V, Caserta E, Poku E, Rockne R, Shively JE, Pichiorri F. Comparison of CD38-Targeted α- Versus β-Radionuclide Therapy of Disseminated Multiple Myeloma in an Animal Model. J Nucl Med. 2021 Jun 1;62(6):795-801. doi: 10.2967/jnumed.120.251983. Epub 2020 Oct 30. PubMed PMID: 33127621; PubMed Central PMCID: PMC8729861.
- Ghose J, Dona A, Murtadha M, Gunes EG, Caserta E, Yoo JY, Russell L, Jaime-Ramirez AC, Barwick BG, Gupta VA, Sanchez JF, Sborov DW, Rosen ST, Krishnan A, Boise LH, Kaur B, Hofmeister CC, Pichiorri F. Oncolytic herpes simplex virus infects myeloma cells in vitro and in vivo. Mol Ther Oncolytics. 2021 Mar 26;20:519-531. doi: 10.1016/j.omto.2021.02.009. eCollection 2021 Mar 26. PubMed PMID: 33738338; PubMed Central PMCID: PMC7940704.
- Lewinsky H, Gunes EG, David K, Radomir L, Kramer MP, Pellegrino B, Perpinial M, Chen J, He TF, Mansour AG, Teng KY, Bhattacharya S, Caserta E, Troadec E, Lee P, Feng M, Keats J, Krishnan A, Rosenzweig M, Yu J, Caligiuri MA, Cohen Y, Shevetz O, Becker-Herman S, Pichiorri F, Rosen S, Shachar I. CD84 is a regulator of the immunosuppressive microenvironment in multiple myeloma. JCI Insight. 2021 Feb 22;6(4). doi: 10.1172/jci.insight.141683. PubMed PMID: 33465053; PubMed Central PMCID: PMC7934939.
- Viola D, Dona A, Caserta E, Troadec E, Besi F, McDonald T, Ghoda L, Gunes EG, Sanchez JF, Khalife J, Martella M, Karanes C, Htut M, Wang X, Rosenzweig M, Chowdhury A, Sborov D, Miles RR, Yazaki PJ, Ebner T, Hofmeister CC, Forman SJ, Rosen ST, Marcucci G, Shively J, Keats JJ, Krishnan A, Pichiorri F. Daratumumab induces mechanisms of immune activation through CD38+ NK cell targeting. Leukemia. 2021 Jan;35(1):189-200. doi: 10.1038/s41375-020-0810-4. Epub 2020 Apr 16. PubMed PMID: 32296125; PubMed Central PMCID: PMC7572537.
- Khalife J, Sanchez JF, Pichiorri F. Extracellular Vesicles in Hematological Malignancies: From Biomarkers to Therapeutic Tools. Diagnostics (Basel). 2020 Dec 9;10(12). doi: 10.3390/diagnostics10121065. Review. PubMed PMID: 33316884; PubMed Central PMCID: PMC7763630.
- Pozhitkov A, Rosenzweig M, Pichiorri F, Gunes EG, Buettner R, Keats JJ, Rosen ST. Glucocorticoid receptor expression in multiple myeloma patients is a predictor of survival. Leuk Lymphoma. 2020 Dec;61(14):3493-3497. doi: 10.1080/10428194.2020.1811860. Epub 2020 Sep 13. PubMed PMID: 32921213; PubMed Central PMCID: PMC7752826.
- Krishnan A, Adhikarla V, Poku EK, Palmer J, Chaudhry A, Biglang-Awa VE, Bowles N, Nathwani N, Rosenzweig M, Sahebi F, Karanes C, Simpson J, Sanchez JF, Yamauchi D, Parayno M, Chowdhury A, Caserta E, Marcucci G, Rockne R, Wu AM, Wong J, Forman SJ, Colcher D, Yazaki P, Shively J, Pichiorri F. Identifying CD38+ cells in patients with multiple myeloma: first-in-human imaging using copper-64-labeled daratumumab. Blood Adv. 2020 Oct 27;4(20):5194-5202. doi: 10.1182/bloodadvances.2020002603. PubMed PMID: 33095874; PubMed Central PMCID: PMC7594407.
- Rosenzweig M, Palmer J, Tsai NC, Synold T, Wu X, Tao S, Hammond SN, Buettner R, Duarte L, Htut M, Karanes C, Nathwani N, Pichiorri F, Sahebi F, Sanchez JF, Chowdhury A, Krishnan A, Forman SJ, Rosen ST. Repurposing leflunomide for relapsed/refractory multiple myeloma: a phase 1 study. Leuk Lymphoma. 2020 Jul;61(7):1669-1677. doi: 10.1080/10428194.2020.1742900. Epub 2020 Apr 8. PubMed PMID: 32268821; PubMed Central PMCID: PMC7384948.
- Khalife J, Ghose J, Martella M, Viola D, Rocci A, Troadec E, Terrazas C, Satoskar AR, Gunes EG, Dona A, Sanchez JF, Bergsagel PL, Chesi M, Pozhitkov A, Rosen S, Marcucci G, Keats JJ, Hofmeister CC, Krishnan A, Caserta E, Pichiorri F. MiR-16 regulates crosstalk in NF-κB tolerogenic inflammatory signaling between myeloma cells and bone marrow macrophages. JCI Insight. 2019 Nov 1;4(21). doi: 10.1172/jci.insight.129348. PubMed PMID: 31593552; PubMed Central PMCID: PMC6948777.
- Buettner R, Morales C, Caserta E, Troadec E, Gunes EG, Viola D, Khalife J, Li H, Keats JJ, Christofferson A, Wu X, Synold TW, Palmer J, Sanchez JF, Pozhitkov A, Vaidehi N, Marcucci G, Krishnan A, Rosenzweig MA, Pichiorri F, Rosen ST. Leflunomide regulates c-Myc expression in myeloma cells through PIM targeting. Blood Adv. 2019 Apr 9;3(7):1027-1032. doi: 10.1182/bloodadvances.2018027227. PubMed PMID: 30940637; PubMed Central PMCID: PMC6457239.