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​Breast Cancer Research Foundation-AACR Career Development Award for Translational Breast Cancer Research

The Breast Cancer Research Foundation-AACR Career Development Awards for Translational Breast Cancer Research represent a joint effort to promote and support innovative research designed to accelerate the discovery, development, and application of new agents to treat breast cancer and/or for preclinical research with direct therapeutic intent. Eligibility is limited to a junior faculty who has completed their most recent doctoral degree or medical residency within the past 11 years. The research proposed for funding must be translational in nature and must have direct applicability and relevance to breast cancer.

2019 Grantees

Jin_LingtaoLingtao Jin, PhD
Assistant Professor
University of Florida College of Medicine
Gainesville, Florida
spacerAGGF1-MCL1 confers paclitaxel resistance in triple-negative breast cancer

Scientific Statement of Research
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that has poor prognosis due to high rate of recurrence. Currently there is no targeted therapy available for TNBC, and taxane-based chemotherapy remains standard of care. Although taxane usually leads to robust clinical response, patients frequently develop drug resistance. Biomarkers that identify responding patients to taxane-based chemotherapy are still lacking. This proposal aims to identify novel protein kinase signaling uniquely required for the resistance of taxane in TNBC through a kinome-wide synthetic lethal screening approach. Identification of such factors will lead to better patient stratification for TNBC. More importantly, we will also develop novel therapeutic agents that may be used to improve current taxane-based therapy in TNBC.

Biography
Dr. Jin is an assistant professor in the department of anatomy and cell biology at the University of Florida. Dr. Jin received his PhD at the Institute of Biophysics, Chinese Academy of Sciences, China. He completed his postdoctoral training in Dr. Sumin Kang’s laboratory at Emory University, focusing on cancer metabolism and protein kinase signaling. Dr. Jin has published many research articles in journals such as Cancer Cell and received awards such as the American Cancer Society Institutional Research Grant. His lab focuses on identification of metabolic signaling in therapy resistance.

Acknowledgment of Support
We have recently established various research platforms to systematically and rigorously study chemo-resistance. Thus, the 2019 Breast Cancer Research Foundation-AACR Career Development Award is invaluable to my career development. It will provide critical support and funding so that I can further investigate the development of chemotherapy resistance in breast cancer.

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Prat_AleixAleix Prat, MD, PhD
Associate Professor
Institute for Biomedical Research August Pi i Sunyer
Barcelona, Spain
spacerTailoring systemic treatment of luminal B breast cancer

Scientific Statement of Research
There is an urgent need to improve our understanding of the biology and treatment response of luminal B breast cancer. In this proposal, we plan to analyze the genomics features of tumor and blood of patients treated in the neoadjuvant setting in a unique phase II clinical trial (SOLTI-1402 CORALLEEN), where approximately 100 patients with luminal B breast tumors have been randomized to six-month standard chemotherapy or endocrine therapy and ribociclib, a CDK4/6 inhibitor. This proposal will help better elucidate the molecular characteristics of luminal B breast cancer and identify biomarkers associated with sensitivity or resistance to chemotherapy versus endocrine therapy in combination with CDK4/6 inhibition. Our main objective is to identify, using molecular and clinical data, the group of patients with luminal B disease who can be cured with targeted therapy without chemotherapy.

Biography
Dr. Prat received his medical degree from the University of Barcelona and became a medical oncologist at Hospital Vall d´Hebron University Hospital in 2008. He then completed a post-doctoral fellowship at the University of North Carolina at Chapel Hill under Dr. Charles M. Perou. In 2012 Dr. Prat returned to Barcelona, where he is currently the head of the medical oncology service at the Hospital Clínic of Barcelona and the head of the translational genomics and targeted therapeutics in solid tumors group at IDIBAPS. He is also a member of the executive boards of the Breast International Group (BIG) and SOLTI, a Spanish clinical trial cooperative group.

Acknowledgement of Support
It is my distinct honor to receive this prestigious and influential grant, which will enable me to find newer and smarter ways to treat luminal B breast cancer. This unique opportunity will also facilitate my career progression to become an independent clinical scientist and accomplish my research goals successfully.

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2018 Grantees

Camila dos Santos, PhDCamila dos Santos, PhD
Assistant Professor
Cold Spring Harbor Laboratory
Cold Spring Harbor, New York
headshot_1 line spacerProbing the immune system to prevent breast cancer development

Scientific Statement of Research
Cancer prevention represents one of the most important challenges of modern medicine. A great deal of evidence suggests that an early pregnancy prevents the development of breast cancer by over 30 percent. This phenomenon is present in several mammalian species and confers a long-lasting cancer protection. However, we know little about the modifications that confer breast cells with a cancer-resistant state. Dr. dos Santos' laboratory studies the mechanisms to prevent breast cancer development. Dr. dos Santos' group previously established that pregnancy changes how breast cells respond to hormones of a second pregnancy. More recently, Dr. dos Santos' group developed a mouse model in which pregnancy can prevent the development of mammary tumors, representing a model of pregnancy-induced breast cancer protection. The Dr. dos Santos group now has insights into the signals that play a role in blocking cancer development in post-pregnancy mammary glands.

Biography
Camila dos Santos obtained a degree in biology (1999) from the Pontifical Catholic University, Brazil. Under the mentorship of Dr. Fernando Ferreira Costa at State University of Campinas, Brazil, she received her masters (2004) and PhD (2007) in molecular and cell biology. In 2008, Dr. dos Santos joined Dr. Gregory Hannon’s group at Cold Spring Harbor Laboratory (CSHL) to study normal and cancerous breast stem cells. In 2015, Dr. dos Santos was promoted as an assistant professor at CSHL. Dr. dos Santos' laboratory uses animal models and genomic analysis to study how pregnancy alters breast cancer risk.

Acknowledgement of Support
During my postdoctoral training, I developed a firm understanding of mammary gland development and epigenomics. Now, I aim to apply my scientific expertise to understand pregnancy-induced breast cancer protection. The support of the 2018 BCRF-AACR Career Development Award will provide the resources to investigate how the immune system interacts with the mammary gland to support cancer prevention.

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Nir London, PhDNir London, PhD
Assistant Professor
Weizmann Institute of Science
Rehovot, Israel
Nir London, PhD 1 line spacerNew targets and new drugs against triple negative breast cancer

Scientific Statement of Research
Breast cancer is the most prevalent and lethal cancer in women. 15% of breast cancers are classified as Triple Negative Breast Cancers (TNBC). TNBCs are more aggressive, has poor prognosis, and lack targeted therapy. This proposal aims to use an electrophilic fragment library to identify TNBC selective molecular targets. The response of TNBC cell lines to various electrophiles will be characterized, in order to elucidate and validate new molecular targets for TNBC, and to develop lead pre-clinical candidates against these targets. In a preliminary screen, a set of fragments that show up to 80-fold selective killing of a TNBC cell line compared to normal breast cells, were identified, with sub-μM IC50. This screening will be expanded to various sub-types of breast cancers and TNBCs. The covalent nature of these compounds will allow to pull down their target proteins and characterize them via proteomics, culminating in the identification of new targets.

Biography
Dr. Nir London, completed his BSc and MSc in 2007, both in computer sciences and computational biology at the Hebrew University of Jerusalem. He completed his PhD at the Hebrew University’s Hadassah Medical School in 2011. Following a postdoctoral fellowship in the Department of Pharmaceutical Chemistry at the University of California, San Francisco (2012-2015), Dr. London joined the Dept. of Organic Chemistry at the Weizmann Institute of Science, as a senior scientist (Asst. Prof). Since 2018, Dr. London is the Incumbent of the Alan and Laraine Fischer Career Development Chair.
 
Acknowledgement of Support
I am deeply honored to be awarded the BCRF-AACR career development award. On the one hand, such international recognition would go a long way to facilitate my career in cancer research, while on the other hand, the generous funding would make it possible to rapidly progress our research.

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2017 Grantees

Smith_90x110.jpg

Bryan R. Smith, PhD
Instructor
Stanford University
Stanford, California
Treatment enhancement via specific manipulation of tumor immunosuppression

Scientific Statement of Research
Recent research has robustly demonstrated that the efficacy of current and emerging cancer treatments is hindered by tumor-mediated immunosuppression effects. Myeloid-derived suppressor cells (MDSCs) play a key role in the maintenance of an immunosuppressive tumor microenvironment that facilitates tumor growth and treatment resistance. We propose to build upon previous work in the nanoprecipitation of albumin-based, drug-loaded nanoparticles (NP) by adding biologic targeting agents to preferentially accumulate NP in myeloid cells. By delivering a payload that is preferentially active in MDSCs, we will specifically inhibit MDSC function, thereby leading to restoration of a competent anti-tumor immune response and increased treatment sensitivity. Our proposed nanoparticle platform was deliberately designed to ease translation. Re-use of FDA-approved drugs in a well-characterized NP architecture and formulation process ensures regulatory familiarity, availability of clinical-grade components, and known safety and side effect profiles.

Biography
Dr. Smith is an instructor in the Department of Radiology and the Molecular Imaging Program at Stanford (MIPS) at Stanford University. He received bachelor's degrees in physics, mathematics, and biomedical engineering. He was awarded a doctorate at The Ohio State University in biomedical engineering as an NSF predoctoral fellow. At Stanford, Dr. Smith has received many awards and published dozens of nanomedicine and oncology articles in journals ranging from Nature Nanotechnology and Nano Letters to Cancer Research and PNAS and has several patents issued and pending. His lab focuses on the development of nano-enabled immuno-imaging and immunotherapy platforms.

Acknowledgement of Support
The 2017 Breast Cancer Research Foundation-AACR Career-Development Award for Translational Breast Cancer Research will be invaluable for my career. It jump-starts my nano-immunotherapy program, making possible data to drive future immuno-oncology grants. More importantly, it fast tracks my team’s passionate interest in rapidly getting our technology to the clinic.

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Danino_90x110.jpg

Tal Danino, PhD
Assistant Professor
Columbia University
New York, New York
Enhancing breast cancer immunotherapies with engineered probiotics

Scientific Statement of Research
This proposal uses novel approaches from synthetic biology to genetically program probiotics to safely deliver therapeutics for breast cancer. Due to their unique property in selectively colonizing tumor necrotic cores, probiotic bacteria can act as specific vehicles for the localized delivery of therapeutics. We will use the probiotic E.coli Nissle 1917, which has been widely and safely tested in humans, to deliver immunotherapeutics to breast cancer metastases. Several therapeutics from the field of immunotherapy will be tested that either activate or recruit the immune system, and efficacy and safety will then be assessed in breast cancer mouse models.

Biography
Tal Danino is an assistant professor of biomedical engineering and leads the Synthetic Biological Systems Laboratory at Columbia University in the City of New York. He received a PhD in bioengineering from the University of California, San Diego, focused on synthetic biology, and completed his postdoctoral training at the Koch Institute for Integrative Cancer Research at MIT where he developed the use of bacteria to detect and treat cancer. In addition to his research, Dr. Danino also brings science outside the laboratory as a TED fellow and through science-art and outreach projects.

Acknowledgement of Support
I am greatly honored to receive the Breast Cancer Research Foundation-AACR Career Development Award. I hope that this award will help build a research framework for engineering probiotics to safely and effectively deliver immunotherapeutics for metastatic breast cancer. 

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