Awardees & Updates – 2024

RECIPIENT: John Hawse, PhD; Mayo Clinic College of Medicine; biochemistry and molecular biology department; co-leader breast and gynecologic cancers program; cancer biology

RESEARCH: Efficacy of a first in class CTPS1 inhibitor for advanced triple negative breast cancer

SUMMARY: Triple negative breast cancer is the most problematic sub-type of breast cancer to effectively treat given its rapid and high recurrence rates, its disproportionate incidence and mortality in young women of minority and underserved populations as well as the overall lack of therapeutic options in the adjuvant and metastatic settings. This study has identified a promising molecule for treating solid tumors in breast, ovarian and endometrial cancers; this study will explore its utility in triple negative breast cancer in models that are sensitive and resistant to standard-of-care therapies.

RECIPIENT: Ilan Remba, MD; Massachusetts General Hospital & Harvard Medical School; neuroendocrine and pituitary tumor clinical center

RESEARCH: Alpha-klotho in patients with acromegaly controlled with somatostatin receptor ligands: association with patient reported outcomes, gonadal function and sex specific differences

SUMMARY: Acromegaly is a chronic disease that results from the hypersecretion of growth hormone (GH) and insulin-like growth factor 1, usually due to a GH-secreting pituitary adenoma. Long-acting injectable somatostatin receptor ligands are the most used therapy to treat this condition, however, patients may report symptoms during and just as the treatment wears off. This study will illuminate most effective course of treatment by examining sex differences to determine best treatment dose and regime.

RECIPIENT: Sol Schulman, PhD; Beth Israel Deaconess Medical Center & Harvard Medical School; division of hemostasis and thrombosis

RESEARCH: An estrogen regulated non-coding RNA regulates the initiation of blood coagulation

SUMMARY: Thrombotic cardiovascular disease, including myocardial infarction (MI), stroke, and venous thromboembolism (VTE), is the leading cause of death among women in the United States. The unique mechanisms contributing to cardiovascular disease in women and the primary mechanism(s) by which estrogens increase VTE risk remain unknown. This lab has initial data that could help explain longstanding uncertainty about how estrogens predispose to cardiovascular disease and suggest that new therapies raising the levels of certain estrogen-related microRNAs to mitigate related thrombotic risk.

RECIPIENT: Lauren Breithaupt, PhD; Massachusetts General Hospital & Harvard Medical School; clinical psychology & neuroscience

RESEARCH: Targeting peripheral and central inflammation with estrogen replacement in women with restrictive eating disorders

SUMMARY: Restrictive eating disorders (R-EDs) including anorexia nervosa are among the most lethal psychiatric illnesses and are highly prevalent in females (1 in 6 females will be diagnosed with R-ED in their lifetime). Less than 50% recover following treatment, underscoring the need for novel treatments. Estrogen deficiency is common in R-EDs and may drive neuroinflammation; estrogen is neuroprotective and alters immune functioning in the brain and periphery. This study seeks to clarify the link between estrogen deficiency (and its replacement), inflammation and core symptoms of R-EDs to guide new treatment.