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Lapo Alinari, MD, PhD


Lapo Alinari, MD, PhD

I was born in Florence, Italy, I graduated from Liceo Scientifico “Gobetti”, (high school) Florence, in July 1991. I started medical school at the University of Florence in October 1991 and received my medical degree with honors in 1998 after defending my dissertation on the biology of hepatocellular carcinoma.

In 1999, I started my residency training in Medical Oncology at the Oncology Department, Malpighi Hospital, Bologna. I spent the first two years of my training primarily working with patients with solid tumors. At the end of my second year, I joined the Hematologic Malignancies Program at the “Seràgnoli” Institute of Hematology and Medical Oncology of the University of Bologna. This was a time when my interest in translational research began to develop. Subsequently, I primarily focused on Non- Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia.

In April 2003, I presented my research dissertation entitled ”Identification of outcome predictors in diffuse large B-cell lymphoma. Immunohistochemical profiling of homogeneously treated de novo tumors with nodal presentation on tissue micro-arrays” and became board certified in Medical Oncology. I then started a Hematology Fellowship program at the “Seràgnoli” Institute of Hematology and Medical Oncology, University of Bologna.

I was enthusiastic and flattered by the invitation (November 2005) offered by Dr. John Byrd to join the outstanding group of scientists he leads at the Ohio State University. My primary focus dealt with discovery and characterization of a novel therapeutic target for lymphoma. In Dr. Baiocchi’s laboratory, I went on to develop this project entitled “Dysregulation of epigenetic mechanisms in Epstein-Barr virus driven lymphomagenesis: role of the protein arginine methyltransferase-5 (PRMT5) and identification of new therapeutic targets” and I decided to use this as the topic of my thesis. I successfully defended my project and went on to receive my degree at the School of Specialty in Hematology from the University of Bologna in November 2007.

Given this strong introduction to basic and translational research, I decided to enroll in a PhD program in Clinical and Experimental Hematology and Hematopathology. I completed my PhD in May 2011.

The highly collaborative scientific atmosphere at Ohio State allowed me multiple opportunities to become involved in several basic, preclinical research projects. I have spent the last ten years of my life training as a cancer research scientist and I decided that The Ohio State University was the best place for me to continue growing as a physician scientist.

I am enrolled in the Physician Scientist Training Program; I completed 2 years of Internal Medicine and I am currently a third year hematology fellow.

Over the past few years, I have developed two major areas of research interest.

The first area of focus involves the basic mechanisms contributing towards the transformation of B lymphocytes. In the laboratory of Dr. Baiocchi, I have developed a model that allows us to examine the genetic and epigenetic events that occur during the B cell transformation process. This model incorporates the Epstein Barr Virus (EBV) that is intimately tied to the pathogenesis of multiple lymphomas occurring in humans. EBV infection occurs worldwide and usually causes no symptoms or relatively brief illness in subjects with an active and efficient immune system. However, immunocompromised patients have a much higher risk to develop this kind of B-cell lymphomas as a consequence of the infection of their lymphocytes by EBV. My area of interest focuses on understanding how the PRMT 5 protein contributes towards the pathogenesis of EBV-induced lymphomas and on trying to identify methods to inhibit this proteins activity in an attempt to inhibit/reverse the B cell transformation process. We have developed an experimental therapeutics program focusing on the synthesis of small molecule inhibitors of PRMT5 and are currently testing several reagents in our laboratory.

My other field of my interest involves preclinical development of novel experimental therapeutic agents for Mantle Cell Lymphoma. I have been focusing my attention on monoclonal antibodies such as Rituximab (anti-CD20), Milatuzumab (anti-CD74) and other agents such as Bortezomib, FTY720, and Silvestrol. Based on my preclinical work, both the anti CD74 and the Bortezomib/Rituximab strategies have been translated into clinical trials treating patients with mantle cell lymphoma here at Ohio State. I have found that witnessing my preclinical research translated to therapies that may offer patients superior care over standard (and ultimately ineffective) treatments to be a rewarding and noble career path to follow.

This was the defining moment that convinced me of my calling to continue my efforts here in the United States to pursue a pathway that would maximize my potential to benefit others, while at the same time, provide a gratifying career pathway.

Over the past ten years I have produced a substantial amount of work that has resulted in the publication of more than 60 papers in peer-reviewed journals including Blood, Journal of Clinical Oncology, Clinical Cancer Research, Oncogene, mAbs, Cancer, Haematologica, and Leukemia & Lymphoma, many invited oral presentations at national and international conferences, the receipt of multiple competitive awards, funding for myself and my mentor. Perhaps more importantly, I have come to the realization that my skills are best suited in a collaborative scientific environment that will promote the translation of my research to meaningful therapies that benefit patients with cancer.

MEMBERSHIP IN PROFESSIONAL SOCIETIES:

-2007 to present: European Hematology Association (EHA)

-2008 to present: American Society of Hematology (ASH)

-2013 to present: American Society of Clinical Oncology (ASCO)

-2013 to present: American Association for Cancer Research (AACR)

AWARDS:

-December 2006: outstanding research project in Haematology (Italian Society of Experimental Haematology).

-January 2008: American Society of Hematology-European Hematology Association International Award.

-October 2011: American Society of Hematology Abstract Achievement Award

-October 2012: American Society of Hematology Abstract Achievement Award

-June 2013: Chairman’s Award for Scholarly Achievement by a Senior Internal Medicine Resident, College of Medicine, The Ohio State University

-June 2013: Clara D. Bloomfield Excellence in Hematology & Oncology Research Award

-November 2013: 2013 Celgene Award for Future Leaders in Hematology

-March 2014: 2014 American Association for Cancer Research Basic Cancer Research Fellowship.

-June 2015: 2015 Excellence in Hematology & Oncology Research Award, Division of Hematology and Medical Oncology, The Ohio State University

OTHER ACHIEVEMENTS:

-Invited abstract reviewer for the 2010 American Society of Hematology Meeting, Category 625-- Lymphoma: Pre-Clinical – Chemotherapy and Biologic Agents.

-Co-Chair for the 2010 American Society of Hematology Meeting, Session: Lymphoma: Pre-Clinical – Chemotherapy and Biologic Agents.

-Invited abstract reviewer for the 2012 American Society of Hematology Meeting, Category 625-- Lymphoma: Pre-Clinical – Chemotherapy and Biologic Agents.

-Co-Chair for the 2012 American Society of Hematology Meeting, Session: Lymphoma: Pre-Clinical – Chemotherapy and Biologic Agents.

-Invited coordinating abstract reviewer for the 2013 American Society of Hematology Meeting, 622A: Non-Hodgkin Lymphoma: Biology, excluding Therapy

-Co-Chair for the 2013 American Society of Hematology Meeting, Session: Non-Hodgkin Lymphoma: Biology, excluding Therapy: Novel Prognostic Factors in Non-Hodgkin's Lymphomas.

-Co-Chair for the 2013 American Society of Hematology Meeting, Session: Non-Hodgkin Lymphoma: Biology, excluding Therapy: Genetic Signature in Non-Hodgkin's Lymphomas.

-Co-Chair for the 2014 American Society of Hematology Meeting, Session: Non-Hodgkin Lymphoma: Biology, excluding Therapy: Molecular Pathogenesis and Prognostic Factors.

-US Patent. No. 8,591,892 issued on Nov 26, 2013. Expiration date: 07/18/2032: FTY720 Increases CD74 Expression and Sensitizes Cancer Cells to Anti-CD74 Antibody-Mediated Cell Death. First named inventor: Lapo Alinari.

-Ad hoc reviewer for Blood, Haematologica, Oncotarget.

PUBLICATIONS:

Chapters in Books:

  1. Alinari L, Porcu P, Coiffier B. Monoclonal Antibodies Therapy for T-cell Lymphomas. In: Foss FM, ed. T-cell Lymphomas. Humana Press; 2012.

Reviews:

  1. Alinari L, Quinion C, Blum K. Bruton’s tyrosine kinase inhibitors in B-cell non-Hodgkin’s lymphomas. Clin Pharmacol Ther. 2015;97(5):469-477.
  2. Alinari L, Christian B, Baiocchi RA. Novel targeted therapies for mantle cell lymphoma. Oncotarget. 2012 Feb;3(2):203-11.
  3. Jaglowski SM, Alinari L, Lapalombella R, Muthusamy N, Byrd JC. The clinical application of monoclonal antibodies in chronic lymphocytic leukemia. Blood, 2010 Nov 11;116(19):3705-14.
  4. Erter J, Alinari L, Darabi K, Gurcan M, Garzon R, Marcucci G, Bechtel MA, Wong H, Porcu P. New Targets of Therapy in T-Cell Lymphomas. Curr Drug Targets, 2010 Apr;11(4):482-93.
  5. Alinari L, Lapalombella R, Andritsos L, Baiocchi RA, Lin T, Byrd JC. Alemtuzumab (Campath-1H) in the treatment of Chronic Lymphocytic Leukemia. Oncogene, 2007 May 28;26(25):3644-53.

Peer reviewed journal articles (selected publications from a total of 56):

  1. Alinari L, Mahasenan KV, Yan F, Karkhanis V, Chung J-H, Smith EM, Quinion Q, Smith PL, Kim L, Patton JT, Lapalombella R, Yu B, Wu Y, Roy S, De Leo A, Pileri S, Agostinelli C, Ayers L, Bradner JE, Chen-Kiang S, Elemento O, Motiwala T, Majumder S, Byrd JC, Jacob S, Sif S, Li C, Baiocchi RA. Selective inhibition of Protein Arginine Methyltransferase 5 blocks initiation and maintenance of B-cell transformation. Blood. 2015; 125(16):2530-43.
  2. Yan F, Alinari L, Lustberg ME, Martin LK, Cordero-Nieves HM, Banasavadi-Siddegowda Y, Virk S, Barnholtz-Sloan J, Bell E,  Wojton J, Jacob NK, Chakravarti A, Nowicki MO, Wu X, Lapalombella R, Datta J, Yu B, Gordon K, Haseley A, Patton JT, Smith PL, Ryu J, Zhang X, Mo X, Marcucci G, Nuovo G, Kwon C-H, Byrd JC, Chiocca A, Li C, Sif S, Jacob S, Lawler S, Kaur B, Baiocchi RA. Genetic validation of the protein arginine methyltransferase PRMT5 as a candidate therapeutic target in glioblastoma. Cancer Research. 2014;74(6):1752-65.
  3. Alinari L, Prince CJ, Edwards RB, Towns WH, Mani R, Lehman A, Zhang X, Jarjoura D, Pan L, Kinghorn AD, Grever MR, Baiocchi RA, Lucas DM. Dual targeting of the cyclin/Rb/E2F and mitochondrial pathways in mantle cell lymphoma with the translation inhibitor silvestrol. Clin Cancer Res. 2012;18(17):4600-11.
  4. Alinari L, Pant S, McNamara K, Kalmar JR, Marsh W, Allen CM, Baiocchi RA. Lymphomatoid granulomatosis presenting with gingival involvement in an immune competent elderly male. Head Neck Pathol. 2012;6(4):496-501.
  5. Alinari L, Baiocchi RA, Prætorius-Ibba M. FTY720-induced blockage of autophagy enhances anticancer efficacy of milatuzumab in mantle cell lymphoma: Is FTY720 the next autophagy-blocking agent in lymphoma treatment? Autophagy. 2012;8(3).
  6. Alinari L, Mahoney E, Patton J, Zhang X, Huynh L, Earl CT, Mani R, Mao Y, Yu B, Quinion C, Towns WH, Chen CS, Goldenberg DM, Blum KA, Byrd JC, Muthusamy N, Praetorius-Ibba M, Baiocchi RA. FTY720 increases CD74 expression and sensitizes mantle cell lymphoma cells to milatuzumab-mediated cell death. Blood. 2011;118(26):6893-903.
  7. Alinari L, Yu B, Christian BA, Yan F, Shin J, Lapalombella R, Hertlein E, Lustberg ME, Quinion C, Zhang X, Lozanski G, Muthusamy N, Praetorius-Ibba M, O'Connor OA, Goldenberg DM, Byrd JC, Blum KA, Baiocchi RA. Combination anti-CD74 (milatuzumab) and anti-CD20 (rituximab) monoclonal antibody therapy has in vitro and in vivo activity in mantle cell lymphoma. Blood. 2011;117(17).
  8. Baiocchi RA, Alinari L, Lustberg ME, Lin TS, Porcu P, Li X, Johnston JS, Byrd JC, Blum KA. Phase 2 trial of rituximab and bortezomib in patients with relapsed or refractory mantle cell lymphoma and follicular lymphoma. Cancer. 2010.
  9. Lucas DM, Alinari L, West DA, Davis ME, Edwards RB, Johnson AJ, Blum KA, Hofmeister CC, Freitas MA, Parthun MR, Wang D, Lehman A, Zhang X, Jarjoura D, Kulp SK, Croce CM, Grever MR, Chen CS, Baiocchi RA, Byrd JC. The novel deacetylase inhibitor AR-42 demonstrates pre-clinical activity in B-cell malignancies in vitro and in vivo. PLoS One. 2010;5(6):e10941.
  10. Liu Q*, Alinari L*, Chen CS, Yan F, Dalton JT, Lapalombella R, Zhang X, Mani R, Lin T, Byrd JC, Baiocchi RA, Muthusamy N. FTY720 Shows Promising In vitro and In vivo Preclinical Activity by Downmodulating Cyclin D1 and Phospho-Akt in Mantle Cell Lymphoma. Clin Cancer Res. 2010 Jun 15;16(12):3182-92.* contributed equally
  11. Majumder S, Alinari L, Roy S, Miller T, Datta J, Sif S, Baiocchi R, Jacob ST. Methylation of histone H3 and H4 by PRMT5 regulates ribosomal RNA gene transcription. J Cell Biochem. 2010;109(3):553-6..
  12. Alinari L, White VL, Earl CT, Ryan T, Johnston JS, Dalton JT, Ferketich AK, Lai R, Lucas DM, Porcu P, Blum KA, Byrd JC, Baiocchi RA. Combination Bortezomib and Rituximab Treatment Affects Multiple Survival and Death Pathways to Promote Apoptosis in Mantle Cell Lymphoma. mAbs 2009;1(1):31-40.
  13. Alinari L, Geskin L, Grady T, Baiocchi RA, Bechtel MA, Porcu P. Subcutaneous alemtuzumab for Sézary Syndrome in the very elderly. Leuk Res. 2008;32(8):1299-303.

INVITED PRESENTATIONS:

INTERNATIONAL:

  1. 53rd Annual Meeting of American Society of Hematology. San Diego, CA, USA, December 10-13, 2011. FTY720 Increases CD74 Expression and Sensitizes Mantle Cell Lymphoma Cells to Milatuzumab-Mediated Cell Death
  2. 50th Annual Meeting of American Society of Hematology. San Francisco, CA, USA, December 6-9, 2008. Combination anti-CD74 (Milatuzumab) and CD20 (Rituximab) Monoclonal Antibody Therapy has In Vitro and In Vivo Activity in Mantle Cell Lymphoma
  3. New Drugs in Hematology. Bologna, Italy, October 9-11, 2005. Gemcitabine (Gemzar): from solid tumors to hematologic malignancies
  4. 5th International Symposium on Special Aspects of Radiotherapy. Berlin, Germany, May 9-11, 2000. Neoadjuvant Hormonotherapy (NHT) and Radiotherapy (RT) in Prostate Cancer

NATIONAL:

  1. Cancer patients and fertility. Ravenna, November 11th, 2005. Lymphoma treatment options in young patients.
  2. Observations in Hematology. Mestre, June 24th, 2005. Monoclonal antibodies in the treatment of B-cell Chronic Lymphocytic Leukemia: “Campath-Rituximab-Zevalin”.
  3. Neuro-oncology - 2° Symposium. Turin, May 23-27, 2005. Non-Hodgkin’s Lymphomas with central nervous system (CNS) involvement.
  4. Non-Hodgkin’s Lymphomas and minimal residual disease: diagnosis and treatment. Naples, December 13-14, 2004. Role of Monoclonal Antibodies in the treatment of minimal residual disease.
  5. Cutaneous Lymphomas: Dermatology or Hematology? Cervia, (Ra), October 2nd, 2004. New drugs development for the treatment of Cutaneous Lymphomas: an update.
  6. Future Directions in Onco-Hematology. Palermo, June 18-19, 2004. Gastrointestinal Non Hodgkin’s Lymphomas.
  7. 79° National Meeting of the Italian Society of Dermatology and Sexually Transmitted Diseases (SIDeMaST). Castellaneta Marina (TA), May 26-29, 2004. Cutaneous Lymphomas: old and new drugs.
  8. Neuro-oncology - 1° Symposium. Turin, May 20th, 2004. Primary central nervous system (CNS) lymphomas. Radiotherapy and chemotherapy.
  9. Italian Association of Radiation Oncology (AIRO). Palermo, November 29th, 2003. Immunotherapy with naked and radio-conjugated monoclonal antibodies in Non-Hodgkin’s Lymphomas
  10. Italian Society of Hematology (SIE). Rome, October 27th, 2003. Front-line treatment of hairy cell leukemia with 2-chlorodeoxiadenosine: long-term outcome.
  11. Non-Hodgkin’s Lymphomas in elderly patients. Milan, November 12th, 2002. High-grade Non-Hodgkin’s Lymphomas in elderly patients.
  12. Annual Meeting of Oncology. Bentivoglio, (Bo), October 9-11, 2000. Role of radiotherapy in relapsed breast cancer patients.
  13. Annual Meeting of Oncology. Bentivoglio, (Bo), October 9-11, 2000. Thromboembolism in cancer patients: preliminary results of a retrospective multicenter national study.