Jose Mazzitelli Perez

MSTP in PhD Training

Program: Neurosciences

Current advisor: Jonathan Kipnis, PhD

Undergraduate university: University of California-Los Angeles, 2017

Enrollment year: 2018

Research summary
Uncovering novel mechanisms of neuroimmune communication

Historically, our lab has focused on understanding how the immune system at the brain’s border, the meninges, impacts CNS function in health and disease. More recently, we discovered that the skull bone marrow surrounding the brain serves as an immune reservoir supplying cells to the underlying meninges. Upon joining the lab, I was interested in understanding 1) is the brain capable of communicating directly to the skull bone marrow and 2) can brain-derived signals mobilize the skull bone marrow in pathological contexts? The first question led to the discovery that cerebrospinal fluid (CSF), which normally bathes the brain and contains brain-derived molecules, can directly access the skull bone marrow. Having developed a method to visualize CSF tracers in vivo, I successfully showed that CSF travels into the skull bone marrow along ossified vascular channels connecting the dural meninges to the bone marrow. Next, transferring CSF from mice with acute spinal cord injury into naïve, healthy mice showed that CNS-derived cues contained within CSF were sufficient to induce immune cell egress from the skull bone marrow to the meninges. Overall, this important work shows that CSF access to skull bone marrow allows the brain to directly communicate with its immune reservoir in context-dependent ways, such as during pathology, to mobilize immune cells to the underlying meninges.

Graduate publications
Mazzitelli JA, Smyth LCD, Cross KA, Dykstra T, Sun J, Du S, Mamuladze T, Smirnov I, Rustenhoven J, Kipnis J. 2022 Cerebrospinal fluid regulates skull bone marrow niches via direct access through dural channels. Nat Neurosci, 25(5):555-60. PMCID: PMC9081158