Roles
Associate Professor
Co-Chair, Research Residency Track Selection Committee in the Department of Dermatology
Group Leader, Skin Cancer Program in Dermatology
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Biography
My research career has centered on the understanding of tumor-specific traits that make cancer therapeutically challenging. As a graduate student in the department of Pathology at the Catholic University in Rome, Italy, I studied the role of oxygen radicals and antioxidant enzymes in cancer growth and progression. After my graduation, I landed a position in the laboratory of Dr. Amato Giaccia in the Department of Radiation Oncology at Stanford University. There, my research focused on understanding how the low oxygen content of tissues, which are normally relatively hypoxic with respect to the atmosphere, promotes cell transformation and ultimately cancer. Following my formative years at Stanford, I obtained my first independent position as assistant professor in the department of biochemistry at Case Western Reserve University in 2009 where I continued my research on the causes of melanoma and the identification of novel therapeutic targets.
I was tenured in 2017, and moved soon after to the University of Miami. Here, my research has continued to focus on the understanding of the the molecular pathways that allow melanoma to grow, survive therapies and propagate to other organs; how these pathways modulate the tumor microenvironment (TME), in particular how melanoma affects immune responses and the relationship between cancer cells and the stroma; and in developing novel treatments that can both overcome resistance to current therapies and also treat a broad range of melanomas independently of their oncogenic drivers (e.g. both BRAF mutated and wild type tumors). From this research we have identified Notch1 as a major co-driver in melanoma pathogenesis and developed a novel anti-Notch1 neutralizing antibody to selectively target this factor. Additionally, my interest has also evolved to the study of brain tumors, particularly glioblastoma multiforme, the most aggressive brain cancer.
We have discovered novel pathways of resistance and DNA Damage Response and have developed new mouse models of disease as well as small molecule inhibitors to target selective factors (e.g. MMP14) involved in resistance. Ultimately, my overarching goal is to dissect the major causes of cancer development and resistance to then tackle these features for therapeutic intervention. -
Education & Training
Education
Post Graduate Training
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Honors & Awards
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Teaching Interests
Since becoming an independent investigator I have been involved with the training of several postdocs, graduate and undergraduate students. My overall goal is to form them in the "art" of science in a tumor biology lab while leveraging their individual strengths. Thus far, most of my trainees have moved on to very fulfilling careers both in academia and industry, and most undergraduates were accepted in medical school, which was their objective. I like to think that I contributed a bit to their success.
Additionally, I have been teaching several classes both at Case Western Reserve University and here at UM. I taught two undergraduate courses, one graduate course and lectured medical students at Case. At UM, I have been involved in teaching in CAB710 (two lectures), MDB765 (one lecture) and in the Master of Science in Skin Biology and Dermatological Sciences (four lectures).
I have taken my role and responsibility as a faculty member at UM very seriously, acting as both a mentor and a role model for students, not only for their research project activities, but also for their career choices and personal matters. I enjoy this aspect of my career and happily contribute to the educational goals of all those students whom I have the ability to help. In short, I really like teaching and transmitting what I know, and do so with enthusiasm. Based on the students evaluation, I think I am doing a good job at it! -
Research Interests
Melanoma: the overarching goal is to discover novel oncogene addictions that can be targeted for therapy, alone or in combination with targeted and immunotherapy. These efforts led us to identify Notch1 as a major oncogene in melanoma capable of controlling several tumor features: growth, metastatic dissemination and response to therapy. Based on this discovery we developed a novel anti-Notch1 neutralizing antibody that is highly selective towards Notch1. This is important as there are other Notch receptors and pan-Notch inhibitors have shown significant toxicity. We are testing our anti-Notch1 antibody both in vitro and in vivo alone and in combination with BRAFis as well as ICIs. We are also expanding our interest to melanoma brain metastasis as this remains a major hurdle in patient survival.
Glioblastoma multiforme (GBM): GBM is the most common and severe form of brain cancer that responds poorly to standard of care (radiation temozolomide) and has shown poor responses to immunotherapy as well. We have identified a novel mechanism of chemoradiation resistance involving the metalloproteinase MMP14 and have developed a novel small molecule inhibitor (ND336) selective against the protein. In preclinical GBM mouse models ND336 in combination with radiation performs better than radiation/temozolomide, the standard of care, and shows great tolerability. MMP14 has also been involved in poor responses to immunotherapy in other cancers. By using a novel GBM mouse model we were able to demonstrate that genetic ablation of MMP14 is sufficient to increase survival likely via a strong anti-tumor immune response in the brain. The goals are therefore to test ND336 in this new model as well as characterize the TME. The overall objectives are to develop new therapies for very aggressive and therapy resistant tumors such as melanoma and GBM. -
Publications
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Professional Activities
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