AICF's 2019-20 Fellows:
Project Abstracts
Margherita Boieri, PhD
Mechanism of CD4+ T cell Mediated Antitumor Immunity
"Thymic stromal lymphopoietin (TSLP) is an epithelial derived factor with the ability to induce the activation of inflammatory CD4+ T helper 2 (Th2) cells and block the early stages of breast cancer development. Understanding the mechanisms involved in Th2 cell-induced tumor immunity, and investigating the changes induced by TSLP-activated Th2 cells within the tumor cells, will give new insights in the previously unrecognized anti-tumor effect of CD4+ Th2 cells. The goal for the second year of this project is to investigate what the mediators are produced by the TSLP-activated CD4+ Th2 and that induce suppression of breast carcinogenesis and to explore their use in cancer treatment and prevention."
Mechanism of CD4+ T cell Mediated Antitumor Immunity
"Thymic stromal lymphopoietin (TSLP) is an epithelial derived factor with the ability to induce the activation of inflammatory CD4+ T helper 2 (Th2) cells and block the early stages of breast cancer development. Understanding the mechanisms involved in Th2 cell-induced tumor immunity, and investigating the changes induced by TSLP-activated Th2 cells within the tumor cells, will give new insights in the previously unrecognized anti-tumor effect of CD4+ Th2 cells. The goal for the second year of this project is to investigate what the mediators are produced by the TSLP-activated CD4+ Th2 and that induce suppression of breast carcinogenesis and to explore their use in cancer treatment and prevention."
Federico Colombo, PhD
Deciphering extracellular vesicle mediated intercellular communication to stop breast cancer
"In 2018 I joined the lab of Dr. Emanuele Cocucci as a post-doctoral researcher at The Ohio State University, to study extracellular vesicle (EV) exchange among cells using imaging approaches. EVs released by the tumor can transform normal cells into malignant ones. With the support of the AICF fellowship I will study how EV communication takes place among breast cancer cells, using lattice light sheet fluorescent microscopy, a revolutionary technology that permits the visualization of living cells in four dimensions. The results of this work can help to design novel therapies for blocking breast cancer metastasis."
Deciphering extracellular vesicle mediated intercellular communication to stop breast cancer
"In 2018 I joined the lab of Dr. Emanuele Cocucci as a post-doctoral researcher at The Ohio State University, to study extracellular vesicle (EV) exchange among cells using imaging approaches. EVs released by the tumor can transform normal cells into malignant ones. With the support of the AICF fellowship I will study how EV communication takes place among breast cancer cells, using lattice light sheet fluorescent microscopy, a revolutionary technology that permits the visualization of living cells in four dimensions. The results of this work can help to design novel therapies for blocking breast cancer metastasis."
Paolo D’Amico, MD
Use of liquid biopsy methods to predict endocrine sensitivity in HR+ metastatic breast cancer
"During my academic years, I was fascinated by the power of non-invasive diagnostic and prognostic systems, as liquid biopsy is.
The aim of the project is to establish ctDNA-based profiles capable to predict endocrine therapy sensitivity and to explore new potential circulating biomarkers, intended to be later extended as markers of early detection of recurrence in primary disease.
Less invasive procedures translate in more acuity in decision-making processes of everyday clinical activity. In my career, I would like to take care of patients affected by breast cancer by making full use of these tools in clinical setting."
Use of liquid biopsy methods to predict endocrine sensitivity in HR+ metastatic breast cancer
"During my academic years, I was fascinated by the power of non-invasive diagnostic and prognostic systems, as liquid biopsy is.
The aim of the project is to establish ctDNA-based profiles capable to predict endocrine therapy sensitivity and to explore new potential circulating biomarkers, intended to be later extended as markers of early detection of recurrence in primary disease.
Less invasive procedures translate in more acuity in decision-making processes of everyday clinical activity. In my career, I would like to take care of patients affected by breast cancer by making full use of these tools in clinical setting."
Rosa Fontana, PhD
Invadopodia regulation in breast cancer invasion and metastasis
"I obtained my PhD in Biology in 2018 at University of Naples Federico II, where I investigated the molecular mechanisms by which the human tumor suppressor p14ARF can perform a pro-oncogenic role in specific cancer cell lines. At UCSD, under the supervision of Dr. Yang, my research project is focused on the study of invadopodia, actin-based structures promoting the ECM degradation during tumor invasion and metastasis. With the support of the AICF Fellowship, I will identify new proteins that regulate invadopodia formation and function with the long-term goal to develop novel therapeutic strategies to selectively inhibit invadopodia-mediated matrix degradation and metastasis in breast cancer."
Invadopodia regulation in breast cancer invasion and metastasis
"I obtained my PhD in Biology in 2018 at University of Naples Federico II, where I investigated the molecular mechanisms by which the human tumor suppressor p14ARF can perform a pro-oncogenic role in specific cancer cell lines. At UCSD, under the supervision of Dr. Yang, my research project is focused on the study of invadopodia, actin-based structures promoting the ECM degradation during tumor invasion and metastasis. With the support of the AICF Fellowship, I will identify new proteins that regulate invadopodia formation and function with the long-term goal to develop novel therapeutic strategies to selectively inhibit invadopodia-mediated matrix degradation and metastasis in breast cancer."
Cristina Guarducci, PhD
Elucidating the mechanisms of resistance to CDK4/6 inhibitors in hormone receptor positive breast cancers
"In 2017 I joined the Dana-Farber Cancer Institute to investigate the mechanisms of resistance to CDK4/6 inhibitors under the mentorship of Dr. Myles Brown and Dr. Rinath Jeselsohn. My research project focuses on estrogen receptor positive breast cancer and aims at studying the evolution of resistance to CDK4/6 inhibitors in cellular and animal models with wild type and mutant estrogen receptor, and exploring whether CDK7 inhibition can be used as a possible strategy to overcome the resistance to CDK4/6 inhibitors."
Elucidating the mechanisms of resistance to CDK4/6 inhibitors in hormone receptor positive breast cancers
"In 2017 I joined the Dana-Farber Cancer Institute to investigate the mechanisms of resistance to CDK4/6 inhibitors under the mentorship of Dr. Myles Brown and Dr. Rinath Jeselsohn. My research project focuses on estrogen receptor positive breast cancer and aims at studying the evolution of resistance to CDK4/6 inhibitors in cellular and animal models with wild type and mutant estrogen receptor, and exploring whether CDK7 inhibition can be used as a possible strategy to overcome the resistance to CDK4/6 inhibitors."
Alice Meroni, PhD
Unravel the mechanism of Topoisomerase I inhibitor resistance
"I am currently doing my post-doc in Alessandro Vindigni’s Lab at Washington University in St. Louis, MO. My studies are mainly focused on defining the resistance pathways activated by cancer cells in response to multiple treatments with the topoisomerase I (TOP1) inhibitor camptothecin (CPT), mimicking a clinical treatment regimen. Thanks to the support of AICF, these results will provide a rationale to target and counteract chemoresistance and also to increase TOP1 inhibitor efficacy."
Unravel the mechanism of Topoisomerase I inhibitor resistance
"I am currently doing my post-doc in Alessandro Vindigni’s Lab at Washington University in St. Louis, MO. My studies are mainly focused on defining the resistance pathways activated by cancer cells in response to multiple treatments with the topoisomerase I (TOP1) inhibitor camptothecin (CPT), mimicking a clinical treatment regimen. Thanks to the support of AICF, these results will provide a rationale to target and counteract chemoresistance and also to increase TOP1 inhibitor efficacy."
Ludovica Monti, PhD
Evaluation of CNS-Active Microtubule-Stabilizing Triazolopyrimidines for the Treatment of Glioblastoma and Other Forms of Cancer
"I received my doctoral degree in Life Sciences from Sapienza University (Rome), during which, I conducted my studies between Italy and USA. My current post-doctoral research at the University of California San Diego aims to apply interdisciplinary sciences, including organic synthesis and biological evaluation of microtubule-targeting agents, to discover novel treatments for central-nervous system disorders, namely, Alzheimer’s disease, and neglected tropical diseases such as, African sleeping sickness. The AICF Post-doctoral Research Fellowship provides a unique platform for me to further develop my research capacity in medicinal chemistry and identify innovative drug candidates for brain tumors and other forms of cancer."
Evaluation of CNS-Active Microtubule-Stabilizing Triazolopyrimidines for the Treatment of Glioblastoma and Other Forms of Cancer
"I received my doctoral degree in Life Sciences from Sapienza University (Rome), during which, I conducted my studies between Italy and USA. My current post-doctoral research at the University of California San Diego aims to apply interdisciplinary sciences, including organic synthesis and biological evaluation of microtubule-targeting agents, to discover novel treatments for central-nervous system disorders, namely, Alzheimer’s disease, and neglected tropical diseases such as, African sleeping sickness. The AICF Post-doctoral Research Fellowship provides a unique platform for me to further develop my research capacity in medicinal chemistry and identify innovative drug candidates for brain tumors and other forms of cancer."
Giovanni Offeddu, PhD
Tumor glycocalyx targeting and its effect on the metastatic cascade
"I am conducting my post-doctoral studies in the research group of Prof. Roger Kamm at MIT, which I joined in April 2017, applying microfluidics techniques to the investigation of cancer and vascular mechanobiology. With the support of the AICF Fellowship, I will study the unique glycocalyx expressed on tumor cells and its interaction with the endothelial glycocalyx across critical stages of the metastatic cascade. The glycocalyx covering tumor cells regulates their interaction with the external environment, and so represents a promising target for cancer therapy."
Tumor glycocalyx targeting and its effect on the metastatic cascade
"I am conducting my post-doctoral studies in the research group of Prof. Roger Kamm at MIT, which I joined in April 2017, applying microfluidics techniques to the investigation of cancer and vascular mechanobiology. With the support of the AICF Fellowship, I will study the unique glycocalyx expressed on tumor cells and its interaction with the endothelial glycocalyx across critical stages of the metastatic cascade. The glycocalyx covering tumor cells regulates their interaction with the external environment, and so represents a promising target for cancer therapy."
Martina Pennisi, MD
Improving suboptimal responses and better defining toxicities and their management in patients treated with CAR T-cells for aggressive lymphomas
“My interest has always been focused on patients with aggressive lymphomas and on the opportunity to improve their outcomes with innovative treatments. In fact, patients with relapsed/refractory disease have dismal outcomes. Recently, Chimeric Antigen Receptor (CAR) Tcells have been approved, but only 30-40% of patients achieve durable complete responses and the majority of patients experience significant toxicities. With Dr. Perales I will work on how to improve responses with the addition of immune-modulating agents in patients who achieve suboptimal responses with CAR T-cells alone, and on better defining toxicities related to CAR Tcells, their predictors and management”.
Improving suboptimal responses and better defining toxicities and their management in patients treated with CAR T-cells for aggressive lymphomas
“My interest has always been focused on patients with aggressive lymphomas and on the opportunity to improve their outcomes with innovative treatments. In fact, patients with relapsed/refractory disease have dismal outcomes. Recently, Chimeric Antigen Receptor (CAR) Tcells have been approved, but only 30-40% of patients achieve durable complete responses and the majority of patients experience significant toxicities. With Dr. Perales I will work on how to improve responses with the addition of immune-modulating agents in patients who achieve suboptimal responses with CAR T-cells alone, and on better defining toxicities related to CAR Tcells, their predictors and management”.
Sara Piccinelli, MD, PhD
Dissecting the hematopoietic stem cell niche and bone marrow regulation of lymphopoiesis
"During my hematology training I was involved in a clinical trial of adoptive immunotherapy with regulatory and conventional T cells in haploidentical hematopoietic stem cell transplantation under the supervision of Prof. Velardi at University of Perugia. During my PhD program I studied how bone marrow regulatory T cells maintain the hematopoietic stem cell niche and control B cell lymphopoiesis. As a Postdoctoral fellow of Dr. Scadden Lab at Massachusetts General Hospital I will further investigate the haematopoietic stem cell niche and the regulation of lymphopoiesis. I will explore how the alteration of bone marrow immune environment impacts on leukemogenesis."
Dissecting the hematopoietic stem cell niche and bone marrow regulation of lymphopoiesis
"During my hematology training I was involved in a clinical trial of adoptive immunotherapy with regulatory and conventional T cells in haploidentical hematopoietic stem cell transplantation under the supervision of Prof. Velardi at University of Perugia. During my PhD program I studied how bone marrow regulatory T cells maintain the hematopoietic stem cell niche and control B cell lymphopoiesis. As a Postdoctoral fellow of Dr. Scadden Lab at Massachusetts General Hospital I will further investigate the haematopoietic stem cell niche and the regulation of lymphopoiesis. I will explore how the alteration of bone marrow immune environment impacts on leukemogenesis."
Pasquale Saggese, PhD
Combination Metabolic-Epigenetic Treatment for Lung Adenocarcinoma
"The AICF Post-Doctoral Research Fellowship will allow me to work at the David Geffen School of Medicine of University of California, Los Angeles, in Dr. Claudio Scafoglio’s laboratory. My research focused on the study of the relationship between cellular metabolism and gene regulation in order to introduce a new potent combination treatment to block the cancer progression from early-stage to more advanced disease. In particular, I’m going to investigate the molecular mechanisms of tumor de-differentiation, induced by SGLT2 inhibition in lung adenocarcinoma, performing pre-clinical tests of combination treatments aimed at preventing the de-differentiation and the development of resistance."
Combination Metabolic-Epigenetic Treatment for Lung Adenocarcinoma
"The AICF Post-Doctoral Research Fellowship will allow me to work at the David Geffen School of Medicine of University of California, Los Angeles, in Dr. Claudio Scafoglio’s laboratory. My research focused on the study of the relationship between cellular metabolism and gene regulation in order to introduce a new potent combination treatment to block the cancer progression from early-stage to more advanced disease. In particular, I’m going to investigate the molecular mechanisms of tumor de-differentiation, induced by SGLT2 inhibition in lung adenocarcinoma, performing pre-clinical tests of combination treatments aimed at preventing the de-differentiation and the development of resistance."
Lucia Sereni, PhD
Editing of the B cell receptor gene: generation of long-living engineered cells factories for on demand production of recombinant antibody as adoptive cancer immunotherapy strategy
"I spent several years in Milano at SR-Tiget, first a PhD student and then Junior Postdoc under the supervision of Dr. Anna Villa, focusing my research on the development new therapeutic strategies for rare genetic diseases.
In 2019 I decided to move to Boston and as an AICF Fellow, I joined the group of Dr. Pietro Genovese at Dan Farber Cancer Institute in Boston. Here, my research will be focused on the development of new immunotherapeutic strategies using advanced genome editing technologies, in order to reprogram the immune system to react against tumour-associated antigens in order to give to cancer patients a long-lasting immune-protection also against tumour relapses."
Editing of the B cell receptor gene: generation of long-living engineered cells factories for on demand production of recombinant antibody as adoptive cancer immunotherapy strategy
"I spent several years in Milano at SR-Tiget, first a PhD student and then Junior Postdoc under the supervision of Dr. Anna Villa, focusing my research on the development new therapeutic strategies for rare genetic diseases.
In 2019 I decided to move to Boston and as an AICF Fellow, I joined the group of Dr. Pietro Genovese at Dan Farber Cancer Institute in Boston. Here, my research will be focused on the development of new immunotherapeutic strategies using advanced genome editing technologies, in order to reprogram the immune system to react against tumour-associated antigens in order to give to cancer patients a long-lasting immune-protection also against tumour relapses."
Sheila Spada, PhD
Role of exosomes derived from irradiated cancer cells in priming of anti-tumor T cells
"After obtaining my PhD in Immunogical Science in Italy, I joined Dr. Demaria at Weill Cornell Medicine, who studies the mechanisms whereby ionizing radiation modulates tumor immunogenicity, and exploiting this property of radiation to achieve a therapeutic synergy with immunotherapy. Thanks to first year of AICF fellowship, I investigated the role of exosomes extracellular vesicles produced by irradiated tumor cells in modulating the immunological microenvironment of breast cancer, and I am going to move forward to study exosome contribution to the priming of anti-tumor immune responses. Results will pave the way to novel vaccination strategies for cancer."
Role of exosomes derived from irradiated cancer cells in priming of anti-tumor T cells
"After obtaining my PhD in Immunogical Science in Italy, I joined Dr. Demaria at Weill Cornell Medicine, who studies the mechanisms whereby ionizing radiation modulates tumor immunogenicity, and exploiting this property of radiation to achieve a therapeutic synergy with immunotherapy. Thanks to first year of AICF fellowship, I investigated the role of exosomes extracellular vesicles produced by irradiated tumor cells in modulating the immunological microenvironment of breast cancer, and I am going to move forward to study exosome contribution to the priming of anti-tumor immune responses. Results will pave the way to novel vaccination strategies for cancer."
Stefano Testa, MD
Reshaping the Tumor Microenvironment to Overcome Resistance towards CpG and anti-OX40 In Situ Vaccination in Aggressive Solid and Hematological Malignancies
“I joined the laboratory of Dr. Ronald Levy, at Stanford University, in January 2019. We study in situ vaccination, an immunotherapeutic strategy that triggers a systemic anti-tumor response through local administration of immune-modulating agents. Specifically, the combination of CpG and anti-OX-40 cures multiple types of cancer in mice. However, some aggressive tumor models exhibit resistance. We selected several molecules that can reshape the tumor microenvironment and, when added to our combination, will hopefully cure even the most resistant cancers. Data from this project will inform the design of clinical trials using the new combinations in multiple solid and hematological malignancies”
Reshaping the Tumor Microenvironment to Overcome Resistance towards CpG and anti-OX40 In Situ Vaccination in Aggressive Solid and Hematological Malignancies
“I joined the laboratory of Dr. Ronald Levy, at Stanford University, in January 2019. We study in situ vaccination, an immunotherapeutic strategy that triggers a systemic anti-tumor response through local administration of immune-modulating agents. Specifically, the combination of CpG and anti-OX-40 cures multiple types of cancer in mice. However, some aggressive tumor models exhibit resistance. We selected several molecules that can reshape the tumor microenvironment and, when added to our combination, will hopefully cure even the most resistant cancers. Data from this project will inform the design of clinical trials using the new combinations in multiple solid and hematological malignancies”
Giulia Zago, PhD
Regulation of tumor-associated phagocyte physiology during tumor cell clearance
“Macrophages are immune cells with the ability to “eat” invasive cells such as bacteria or cancer cells and stimulate a subsequent immune response against this threat. This clearance process is crucial to maintaining the health of our tissues, but in the case of cancer, this mechanism is being exploited to contain the immunologic response. Working in Dr. Perry lab at Memorial Sloan Kettering Center, and supported by AICF, I am trying to elucidate the mechanistic behind engulfment of cells by macrophages and its relationship with tumor development. Our final goal is to improve the effectiveness of immunotherapy for cancer patients."
Regulation of tumor-associated phagocyte physiology during tumor cell clearance
“Macrophages are immune cells with the ability to “eat” invasive cells such as bacteria or cancer cells and stimulate a subsequent immune response against this threat. This clearance process is crucial to maintaining the health of our tissues, but in the case of cancer, this mechanism is being exploited to contain the immunologic response. Working in Dr. Perry lab at Memorial Sloan Kettering Center, and supported by AICF, I am trying to elucidate the mechanistic behind engulfment of cells by macrophages and its relationship with tumor development. Our final goal is to improve the effectiveness of immunotherapy for cancer patients."
