Cottini395 W. 12th Ave., Third Floor
Columbus, OH 43210
Francesca.Cottini@osumc.edu

I grew up in a small village of 3,000 inhabitants on the shore of Lago Maggiore in Italy. I attended medical school at Universita' Vita - Salute San Raffaele in Milan. For my graduation thesis, I worked under the supervision of Dr. Paolo Ghia and Dr. Caligaris-Cappio on Monoclonal B cell lymphocytosis. I was co-author of two publications in blood and cytometry B clin cytometry. After graduating in 2009, I moved to Boston, thanks to a fellowship grant from Cariplo Foundation, and started working as a post-doctoral fellow in the laboratory of Dr. Kenneth Anderson, a world-known expert of multiple myeloma and future president of the American Society of Hematology.

Under his supervision, I published two first author publications and co-authored several other manuscripts. Specifically, one manuscript was published in 2014 in Nature Medicine, showing that YAP1, a transcriptional regulator of the Hippo pathway, is an essential factor in the control of apoptosis upon DNA damage in multiple myeloma and in other hematological malignancies. Re-activation of YAP1 by serine-threonin 4 (STK4) inhibition causes growth inhibition and apoptosis in hematological malignancies. These discoveries were highlighted in Nature Medicine, Cancer Discovery and Molecular and Cellular Oncology and endorsed in a U.S. patent. Specific STK4 inhibitors are under development thanks to collaborative LLS grant and to a personal IMF fellowship. Another original work has just been published in Cancer Discovery, demonstrating that replicative stress, a condition associated with incomplete or aberrant DNA synthesis at the level of fork replications, is present in multiple myeloma and causes together with oxidative stress ongoing DNA damage in a subset of patients with poor prognosis. Strategies coupling inhibition of DNA repair and induction of oxidative stress to trigger DNA damage represent a potent synthetic lethality approach in this cohort of patients with otherwise unfavorable outcomes.
 
Among other achievements, I was a 2014 TRTH trainee, selected among the 20 top applicants from all over the world, and a past Daryl Elizabeth Layzer fellow and a current IMF fellow. I have won the ASH abstract achievement award, twice, and presented several times at the American Society of Hematology meetings and European Hematology Association meetings. I wrote three book chapters on multiple myeloma, one that will be published in the next edition of Williams’ Hematology book, and have three U.S. patents and several other publications as co-authors.

However, when I was in the lab, I was missing my clinic time. I adore spending time with my patients and think that it is really important for physician-scientists to have a strong research background but also an extensive clinical knowledge. Specific clinical cases can indeed trigger interesting ideas to be studied in the lab. Vice versa, the dream of every physician scientist is to apply what she or he is studying in the lab to real people and not just to cultured cells.

This duality between clinic and research triggered the decision to apply for internal medicine residency training. From May 2014, I started spending more time in the outpatient clinic with Drs. Kenneth Anderson and Paul Richardson. When I applied in September for internal medicine training, the Physician Scientist Training Program (PSTP) at OSU immediately stood out among the other choices. Indeed, the PSTP program will give me the possibility of combining the love for patient care with the strength and excellence in research at OSU. OSU is the house of several great hematologists, whose roles are well-recognized in the field with several high-level publications, funded grants and awards. Additionally, the new James Cancer Hospital is welcoming, amazing and can really make a difference in cancer care. Therefore, the vibrant scientific and clinic community is a great plus for future physician scientists like me.

I immediately felt at home with everybody during the interview day, a feeling that also persists now that I have started my training. We work hard but the collegial atmosphere among the residents, fellows, attendings, nurses and PCAs helps the day go smoothly. Moreover, we have several educational tools, including morning and afternoon conferences, procedural skill sessions and online modules to complete. As far as I have experienced, the program is a great balance between educational and clinical activities.

Columbus is also a great city. The food scene is vibrant, with a vast choice of breweries, food trucks and restaurants. There are also great outdoor activities, with several parks and bicycle circuits. Additionally, the city is way cheaper than Boston!

Certifications and licensures:

Temporary Ohio Medical Board license
ACLS - BLS

Education:

Internal Medicine Resident (Physician Scientist Track Program), The Ohio State University, 2015 - present

MD: Vita-Salute S. Raffaele University, 2009
  • Thesis title: “Monoclonal B cell Lymphocytosis in the healthy adult population. Molecular analysis and risk of evolution into CLL” 
  • Advisor: Drs. Paolo Ghia and Federico Caligaris Cappio 
  • Honors: 110/110 cum laude and honors

Honors:
  • Young Fellow Award (International Myeloma Foundation), 2015
  • TRTH participant (EHA-ASH translational research training in hematology), 2014-2015
  • Career Development Award (Specialized program of research excellence, 2014
  • Daryl Elizabeth Layzer fellow, 2014
  • AACR Scholar-in-Training Award (AACR), 2014
  • Rowena and Charles Simberg Family Award - Excellence in hematology research, 2014
  • Abstract Achievement Award Recipient (ASH), 2014
Professional activities:
  • Gold Humanism Honor Society – OSU chapter
  • American Association for Cancer Research – Women in Cancer Research chapter
  • American Society of Hematology – TRTH scholar
  • European Hematology Association – TRTH scholar
  • American Medical Association
  • American College of Physicians
  • American Society of Clinical Oncology
  • Italian medical board, chapter of Novara
  • NEJM group discussion moderator
  • Medpage expert on novel targets in multiple myeloma

Editorial Responsibilities

  • Blood (reviewer)
  • Oncogene (reviewer)
  • Expert Opinion On Therapeutic Targets (reviewer)
  • Pharmacological Research (reviewer)
  • Italian Ministry of Health (grant reviewer)
  • Fondazione di Padova e Rovigo (grant reviewer)

Educational Activities

Teaching activities

  • Clinical instructor, internal medicine – teaching and supervision of MS3- MS4 and PGY1 residents in inpatient and outpatient settings
  • Tutor for MS1 for cell biology between 2004 - 2006 at Universita’ Vita-Salute San Raffaele, Milan, Italy

Advising and supervision

  • Ahaana Singh, Dana- Farber Cancer Institute, Mentoring of high school student sophomore during her summer experience in a research lab 
  • Trudy Wu, internal medicine resident/medical student mentoring program, mentor

Grants

  • INTERNATIONAL MYELOMA FOUNDATION- 2015 Brian D. Novis Research Award 
  • Junior Grant Application- Principal Investigator: Kenneth C Anderson
    Title: Targeting the kinase STK4 to treat myeloma
    Description: Investigation of mechanisms of action of STK4 inhibition in cellular and animal models
    $50,000: $45,000 as direct costs and $5,000 as indirect costs
    Role: Principal Investigation (50% effort)

Patents

  • Compositions and methods for treating multiple myeloma - U.S. provisional patent application No. 62/074,935
  • Novel targets in multiple myeloma and other disorders - WO 2014068542 A1
  • STK4 inhibitors for treatment of hematological malignancies - U.S. provisional patent application No. 62/140,695

Publications

Peer-reviewed publications

  • Hideshima T, Cottini F “p53-related protein kinase confers poor prognosis and represents a novel therapeutic target in multiple myeloma” Blood. 2017 Jan 12. pii: blood-2016-09-738500. doi: 10.1182/blood-2016-09-738500
  • Cottini F, Suzuki R, Hideshima T, Anderson K and Tonon G. “Synthetic lethal approaches exploiting replicative stress in aggressive myeloma”. Cancer Discovery. 2015, Sep; 5(9):972-87
  • Cottini F, Hideshima T, Xu C, Sattler M, Neri A, Ponzoni P, Richardson P, Carrasco R, Kimmelman A, Wong K, Caligaris-Cappio F, Blandino G, Kuehl M, Anderson K and Tonon G. “Rescue of Hippo co-activator YAP1 triggers DNA damage-induced apoptosis in hematological cancer” Nature medicine. 2014, Jun; 28(3): 599-606
  • Malek E, Abdel-Malek M, Jagannathan S, Vad N, Van Duin M, Sonneveld, Cottini F, Anderson K, Driscoll J “Pharmacogenomics and chemical library screens reveal a novel SCFSKP2 inhibitor that overcomes Bortezomib resistance in multiple myeloma”. Leukemia. 2016, Nov 4. doi: 10.1038/leu.2016.258 [Epub ahead of print]
  • Hideshima T, Qi J , Paranal R, Tang W, Greenberg E, West N, Colling M, Mazitschek R, Perry J, Ohguchi H, Cottini F , Mimura N, Görgün G, Richardson P, Wiest O, Anderson KC , Bradner J “Discovery of selective small-molecule HDAC6 inhibitors for overcoming proteasome inhibitor resistance in multiple myeloma” Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):13162-13167
  • Suzuki R, Kikuchi S, Harada T, Mimura N, Minami J, Ohguchi H, Yoshida Y, Sagawa M, Gorgun G, Cirstea D, Cottini F, Jakubikova J, Tai YT, Chauhan D, Richardson PG, Munshi N, Ando K, Utsugi T, Hideshima T, Anderson KC. “Combination of a Selective HSP90α/β Inhibitor and a RAS-RAF-MEK-ERK Signaling Pathway Inhibitor Triggers Synergistic Cytotoxicity in Multiple Myeloma Cells”. PLoS One. 2015 Dec 2;10(12): e0143847
  • Hideshima T, Cottini F, Ohguchi H, Jakubikova J, Gorgun G, Mimura N, Tai YT, Munshi NC, Richardson PG, Anderson KC. “Rational combination treatment with histone deacetylase inhibitors and immunomodulatory drugs” Blood Cancer J. 2015, May; 5: e312
  • Kikuchi S, Suzuki R, Ohguchi H, Yoshida Y, Lu D, Cottini F, Jakubikova J, Bianchi G, Harada T, Gorgun G, Tai YT, Richardson PG, Hideshima T, Anderson KC. “Class IIa HDAC inhibition enhances ER stress-mediated cell death in multiple myeloma” Leukemia. 2015, Sep; 29(9): 1918-1927
  • Suzuki R, Hideshima T, Mimura N, Minami J, Ohguchi H, Kikuchi S, Yoshida Y, Gorgun G, Cirstea D, Cottini F, Jakubikova J, Tai YT, Chauhan D, Richardson PG, Munshi NC, Utsugi T, Anderson KC. “Anti-tumor activities of selective HSP90α/β inhibitor, TAS-116, in combination with bortezomib in multiple myeloma” Leukemia. 2015, Feb; 29(2): 510-4
  • Mimura N, Hideshima T, Shimomura T, Suzuki R, Ohguchi H, Rizq O, Kikuchi S, Yoshida Y, Cottini F, Jakubikova J, Cirstea D, Gorgun G, Minami J, Tai YT, Richardson PG, Utsugi T, Iwama A, Anderson KC. “Selective and potent Akt inhibition triggers antimyeloma activities and enhances fatal endoplasmic reticulum stress induced by proteasome inhibition” Cancer Res. 2014, Aug; 74(16): 4458-69
  • Minami J, Suzuki R, Mazitschek R, Gorgun G, Ghosh B, Cirstea D, Hu Y, Mimura N, Ohguchi H, Cottini F, Jakubikova J, Munshi NC, Haggarty SJ, Richardson PG, Hideshima T, Anderson KC. “Histone deacetylase 3 (HDAC3) as a novel therapeutic target in multiple myeloma.” Leukemia. 2014 Mar; 28(3): 680-689
  • Cirstea D, Hideshima T, Santo L, Eda H, Mishima Y, Nemani N, Hu Y, Mimura N, Cottini F, Gorgun G, Ohguchi H, Suzuki R, Loferer H, Munshi NC, Anderson KC, Raje N. “Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs.” Leukemia. 2013 Dec;27 (12): 2366-75
  • Cea M, Cagnetta A, Fulciniti M, Tai YT, Hideshima T, Chauhan D, Roccaro A, Sacco A, Calimeri T, Cottini F, Jakubikova J, Kong SY, Patrone F, Nencioni A, Gobbi M, Richardson P, Munshi N, Anderson KC. “Targeting NAD+ salvage pathway induces autophagy in multiple myeloma cells via mTORC1 and extracellular signal-regulated kinase (ERK1/2) inhibition”. Blood. 2012, Oct; 120(17): 3519-29
  • Fazi C, Scarfò L, Pecciarini L, Cottini F, Dagklis A, Janus A, Talarico A, Scielzo C, Sala C, Toniolo D, Caligaris-Cappio F, Ghia P. “General population low-count CLL-like MBL persist over time without clinical progression, though carrying the same cytogenetic abnormalities of CLL”. Blood. 2011, Dec; 118(25): 6618-25
  • Fazi C, Dagklis A, Cottini F, Scarfò L, Bertilaccio MT, Finazzi R, Memoli M, Ghia P. “Monoclonal B cell Lymphocytosis in HCV-infected individuals” Cytometry B Clin Cytom. 2010, Jan; 78(Suppl 1:S61): S61-8

Submitted manuscripts

  • Cottini F, Sborov D, Cho Y, Lamprecht M, Tackett K, Li J, Devine S, Poi M, Phelps M, Hofmeister C “G-CSF Starting Day +1 after Autologous Transplant Is Safer Than Day +5 or Day +7 in Patients with Multiple Myeloma” Leuk Lymphoma. Under revision
  • Cottini F, Dungan K DKA following pembrolizumab infusion“ Book “Atypical/Rare forms of diabetes”

Reviews

  • Cottini F, Anderson KC. “Novel therapeutic targets in multiple myeloma” Clin Adv Hematol Oncol. 2015, Apr; 13(4): 236-48
  • Cottini F, Anderson KC and Tonon G. “Awakening the Hippo co-activator YAP1, the mercurial cancer gene, in hematological cancer.” Molecular & Cellular Oncology. 2014, Dec; 1(3)
  • Cottini F, Lautenschlaeger T. “Predictors of biomarkers guiding targeted therapeutic strategies in locally advanced lung cancer”. Cancer J. 2013, Jun; 19(3):263-71

Books and chapters

  • Cottini F, O'Donnell E, Raje N, and Anderson KC (2015). Chapter 107: Myeloma. In Marshall A. Lichtman, Thomas J. Kipps, Uri Seligsohn, Kenneth Kaushansky, Josef T. Prchal (Ed 9th), Williams Hematology, Ninth Edition (pp 1737-1772) McGraw-Hill Professional
  • Cottini F, Guidetti A, Paba-Prada C, Hideshima T, Maglio M, Varga C, Chauhan D, Laubach J, Anderson KC, and Richardson P (2014). In Q.P.Dou (Ed 1st), Resistance to Proteasome Inhibitors in Cancer: Molecular Mechanisms and Strategies to Overcome Resistance, (pp47-80). Springer
  • Cottini F, Tonon G, and Anderson KC (2014). Chapter 18: Genomics in Multiple Myeloma: From Conventional cytogenetics to Novel Whole Genome Sequencing approaches. In Dellaire G, Berman J and Arceci RJ (Ed 1st), Cancer Genomics: From Bench to Personalized Medicine, (pp302-316). Elsevier

Non-print Materials

Presentations and Abstracts

Invited presentations

“Targeting DNA damage in multiple myeloma”. Methodist Houston Hospital, Houston, TX.January 2015

Oral presentations (speaker) - national and international meetings

“Synthetic lethal approaches to exploit replicative stress in aggressive Myeloma”. 56th American Society of Hematology Annual meeting and Exposition, San Francisco, Session: 651. Myeloma - Biology and Pathophysiology, excluding Therapy: Mechanisms of Drug Resistance and Genomic Instability in Myeloma. Session Date and Time: Sunday, December 7, 2014: 5:30 p.m.

“Serine/Threonine kinase STK4 is a novel target in Myeloma” 56th American Society of Hematology Annual meeting and Exposition, San Francisco. Session Name: 652 Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Signal Transduction in Myeloma Monday, December 8, 2014: 5 p.m.

“Exploiting oncogene-induced DNA replicative stress as synthetic lethal approach to target myeloma” AACR Special Conference: Hematologic Malignancies: Translating Discoveries to Novel Therapies, Philadelphia. Concurrent Session 2: Myeloma. Session Date and Time: Monday, September 22, 2014 from 10:30 a.m. - 12:30 p.m.

“Inhibition of the STK4 kinase restores the Hippo co-factor YAP1 and induces DNA- Francesca Cottini, MD damage mediated apoptosis in multiple myeloma cells” 10th Annual Postdoc and Graduate Student Dana-Farber Cancer Institute; Boston, MA. Session time: Thursday, September 18, 2014 from 1.30 p.m.

Inhibition of the STK4 kinase restores the hippo co-factor YAP1 and induces DNAdamage mediated apoptosis in multiple myeloma cells” 19th Congress of the European Hematology Association, Milan, Session: Myeloma and other monoclonal gammopathies – Biology; Date of presentation: Saturday, June 14 2014: 4:45 p.m.

The Oncogene MYC Triggers Replicative Stress and DNA Damage In Multiple Myeloma” International Myeloma Foundation (IMF) webcast interview selected, ASH meeting 2013, New Orleans

A novel target to treat hematopoietic malignancies” Italian Scientists and Scholars of North America Foundation Annual Meeting, Paola Campese Award, Italian Embassy in Washington, DC October 29th 2013

The Role of the ABL1/YAP1/P73 Axis in Prevention of DNA Damage-Mediated Apoptosis in Multiple Myeloma”54th American Society of Hematology Annual meeting and Exposition, Atlanta, Session: 651. Myeloma - Biology and Pathophysiology, excluding Therapy: New Insights into Myeloma Biology from Clonogenic Cells to Circulating Tumor Cells Monday, December 10, 2012: 5:30 p.m.

Poster presentations (presenter) - national and international meetings

Francesca Cottini, Teru Hideshima, Giovanni Tonon, and Kenneth Anderson (2015). “Exploiting oncogene-induced DNA replicative stress as synthetic lethal approach to target myeloma” (American Society of Hematology meeting, 2015, Orlando)

Francesca Cottini, Teru Hideshima, Giovanni Tonon, and Kenneth Anderson (2014). “Exploiting oncogene-induced DNA replicative stress as synthetic lethal approach to target myeloma” (AACR Special Conference: Hematologic Malignancies: Translating Discoveries to Novel Therapies; 2014, Philadelphia, PA)

Paolo Ghia, Claudia Fazi, Lorenza Pecciarini, Lydia Scarfò, Francesca Cottini, Antonis Dagklis, Agnieszka Janus, Cristina Scielzo, Cinzia Sala, Daniela Toniolo, and Federico Caligaris-Cappio “CLL-Like MBL In the General Population Persist Over Time, without Clinical Progression, Though Carrying the Same Cytogenetic Abnormalities of CLL” (American Society of Hematology meeting, 2010, Orlando)

Francesca Cottini, Teru Hideshima, Chunxiao Xu, Paul G. Richardson, Alec C. Kimmelman, Kwok K. Wong, Federico Caligaris Cappio, Kenneth C. Anderson and Giovanni Tonon “Rescue of YAP1 triggers DNA damage-induced apoptosis in hematological cancers” San Raffaele retreat 28th November 2013, Milan, Italy

Francesca Cottini, Teru Hideshima, Giovanni Tonon and Kenneth C. Anderson “The Oncogene MYC Triggers Replicative Stress and DNA Damage In Multiple Myeloma” (American Society of Hematology meeting, 2013, New Orleans)

Community Service

  • Dana - Farber Cancer Institute, volunteer for Shadow Day. Opportunity for high school students and donors to shadow a researcher in her working day Italian Medical Board - flu vaccination campaign 

Language Competence

  • Native Italian speaker
  • Fluent in English
  • Intermediate proficiency in French and basic knowledge of Spanish
Appointments

Appointments

Clinical Instructor June 2015 - present

Department of Internal Medicine, The Ohio State University, Columbus, OH

Postdoctoral Fellow/Scholar August 2010 - May 2015

Supervisor: Kenneth Anderson, Giovanni Tonon and Teru Hideshima

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA

Projects:
  • Evaluation of the role of YAP1 and Hippo pathway in multiple myeloma
  • Mechanism of DNA damage and replicative stress in multiple myeloma
  • Mechanisms of action and resistance to lenalidomide treatment

Postdoctoral Fellow/Scholar February 2010 - July 2010

Supervisor: Giovanni Tonon and Paolo Ghia

Division of Molecular Oncology, San Raffaele Scientific Institute, Milan, Italy

Projects:

  • Evaluation of the role of YAP1 in multiple myeloma pathogenesis
  • Characterization of monoclonal B cell lymphocytosis in the healthy population

Clinical Clerk September 2014

Supervisor: Dr. Ephraim Hochberg and Dr. Edwin Choy

Massachusetts General Hospital Cancer Center, Boston

Clinical Trainee 2014 - 2015

Supervisor: Dr. Paul Richardson and Dr. Kenneth C Anderson

Multiple Myeloma Program, Dana-Farber Cancer Institute, Boston