This month we are highlighting two awards: Dr. Ana Soto, funded by the University of Utrecht for her project “Female Reprotoxicity of EDCs: a human evidence-based Screening and Identification Approach” and Dr. Srivalleesha Mallidi, funded by the National Institutes of Health via Massachusetts General Hospital as a part of the project “Dual function theranostic constructs for photoacoustic guided surgery and photodynamic therapy.” Please see the abstracts for these proposals below.
PI: Ana Soto
Funder: University of Utrecht
Title: Female Reprotoxicity of EDCs: a human evidence-based Screening and Identification Approach
Abstract: The main objective of this project, named FREIA, is to provide a human relevant, mechanism-based testing strategy with validated test models to reliably predict female reproductive toxicity related to exposure to environmental chemicals with endocrine activity (endocrine disrupting chemicals, EDC) during sensitive windows of development. A woman’s ability to have children directly depends on (the development of) correctly functioning ovaries. However, limited information is available on the mechanisms by which exposure to EDCs during specific windows of exposure, i.e. during development, puberty or adult age, may impair female reproduction. In this project, the effect of EDCs in fetal and pubertal rat exposure scenarios are compared with regards to later-onset adult effects including changes in ovarian histology, follicle counts and regularity of estrous cycles. Effect biomarkers from rodent studies will be compared with human effect biomarkers from studies with human fetal tissues and human oocytes from different age groups. Mechanistic knowledge on the biological processes underlying female reproductive toxicity will be described to frame provisional adverse outcome pathways (AOPs), which will be the basis to map existing test systems into an Integrated Approach to Testing and Assessment (IATA). Novel test methods will be developed to cover potential gaps in current test methods to address female reprotoxicity.
PI: Srivalleesha Mallidi
Funder: National Institutes of Health, via Massachusetts General Hospital
Title: Dual function theranostic constructs for photoacoustic guided surgery and photodynamic therapy
Abstract: Survival rates in patients with oral cavity tumors have remained nearly stagnant in the past decade with exceptional morbidity e.g., tongue cancers. The goal of this Academic-Industry Partnership (AIP) application is to develop, for the first time, a single theranostic agent namely targeted Dual Function Antibody Conjugate (DFAC) amenable to deep tissue photoacoustic imaging (PAI) with targeted photodynamic therapy (PDT), and an integrated PAI-ultrasound imaging (USI) module for surgery guidance such that the two main barriers to oral cancer treatment outcomes are overcome. Difficulty in gauging the depth of tumor invasion during surgical resection and residual microscopic disease are the two main barriers responsible for the high loco-regional recurrence rates in oral cavity tumors. Cautionary removal of extra normal tissue leads to functional loss and a compromised quality of life. Through this AIP grant, we establish a collaborative framework between the academic research labs of Dr. Tayyaba Hasan at Massachusetts General Hospital (MGH), Dr. Srivalleesha Mallidi at Tufts University, the clinical Otolaryngology surgical team of Drs. Mark Varvares and Meredith August at Mass Eye and Ear Infirmary and MGH, and the Akita Innovations industry team, to create a comprehensive theranostic solution that enables deep tissue image-guided, normal tissue-sparing surgery and tumor-targeted spatially-localized therapy in the oral cavity. Our synergistic scientific expertise, respective infrastructures, clinical translation experience and geographic proximity position us well to achieve our goals. Relevance: The study offers deep tissue imaging and targeted therapy in a single intraoperative session, resulting in lower recurrence, lower cost, higher overall survival and improved quality of life. The modular design of DFAC and integrated PAI-US, enables adaptation of the platform to other cancers.