Research
The Boire laboratory investigates the leptomeningeal space. The leptomeninges, layers of membranous. coverings, encase the central nervous system and contain the circulating cerebrospinal fluid (CSF). In health, the leptomeninges maintain neural homeostasis and provide a route of biochemical communication between the periphery and the central nervous system. In disease, the leptomeningeal space plays host to a variety of pathologies, including autoimmunity, infectious disease, and malignancy. While each project in the lab investigates a different aspect of the leptomeninges, we are all passionate about the biology of this space... We love CSF!
Cancer cells may spread nearly anywhere in the body. When they enter into and grow within the leptomeningeal space, leptomeningeal metastasis (LM) results. This complication of cancer wreaks havoc with the homeostatic capacities of the CSF leading to neurological disabilities and death. We seek to understand neuroanatomically where and mechanistically how cancer cells become competent to enter into the leptomeninges. Once within the leptomeninges, cancer cells face profound metabolic challenges including low extracellular iron, hypoxia, and low extracellular lipid. We investigate how cancer cells overcome these metabolic constraints so that we may interrupt this signaling and arrest cancer cell growth in the space.
Although classically viewed as a barrier system, a more modern view of the leptomeninges is that of a conduit for biochemical and cellular communication between the systemic circulation and the central nervous system. Immune cells, their mediators, as well as signaling molecules generated from extra-CNS tissues are all detectable within the CSF. We investigate this signaling with the goal of understanding and ultimately interrupting neuro-pathological processes at the whole-organism level. This includes metastasis, autoimmunity, and infection.
Current Projects:
- Cancer cell selection and dormancy
- Metabolic adaptation of cancer cells
- Cancer cell interactions with the cortical surface
- Immunology of the leptomeningeal space
- Biochemical communication across blood-brain-barriers
Bio
Dr. Boire earned her BA at Macalester College and then pursued graduate training in Biochemistry at Tufts University, where she earned a PhD. Inspired to pursue a career as a physician-scientist, she obtained her medical degree at the University of Chicago Pritzker School of Medicine. This was followed by clinical residency in Neurology at the Neurologic Institute (Columbia University) and Neuro-Oncology fellowship at Memorial Sloan Kettering Cancer Center. Scientifically, she carried out postdoctoral training under the mentorship of Joan Massagué before joining faculty at MSKCC in the Neurology Department, Human Oncology and Pathogenesis Program, and Cornell’s BCMB Program.
Distinctions:
- Elected Fellow American Academy of Neurology (2023)
- Pershing Square Sohn Prize (2019)
- Pew Biomedical Scholar (2018)
- Damon Runyon Clinical Investigator Award (2017)
Selected Publications:
Remsik J, Saadeh F, Tong X, Li M-J, Snyder J, Bale T, Wu J, Derderian C, Guber D, Chi Y, Murali R, and A Boire.. 2021 Characterization, isolation and in vitro culture of leptomeningeal fibroblasts. J Neuroimmunol. 361:577727. (https://pubmed.ncbi.nlm.nih.gov/34688068/)
Remsik J, Wilcox JA, Babady NE, McMillen TA, Vachha BA, Halpern NA, Dhawan V, Rosenblum M, Iacobuzio-Donahue CA, Avila EK, Santomasso B and A Boire 2021 Inflammatory leptomeningeal cytokines mediate COVID-19 neurologic symptoms in cancer patients Cancer Cell 39(2):276-283. (https://pubmed.ncbi.nlm.nih.gov/33508216/)
Chi Y, Remsik J, Kiseliovas V, Derderian C, Sener U, Alghader M, Saadeh F, Nikishina K, Bale T, Iacobuzio-Donahue C, Thomas T, Pe’er D, Mazutis L and A Boire 2020 Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis. Science 369(6501):276-282. (https://pubmed.ncbi.nlm.nih.gov/32675368/)
Boire A, Zou Y, Shieh J, Macalino D, Pentsova E and J Massagué. 2017 Complement Component 3 Adapts the Cerebrospinal Fluid for Leptomeningeal Metastasis. Cell 168(6):1101-1113. (https://pubmed.ncbi.nlm.nih.gov/28283064/)