Decoding blood and brain crosstalk

We study the dialogue of molecules and immune cells between brain and body. We aim to understand what these messages mean, how they’re regulated, and how they shape brain aging and disease. We combine chemical biology, neuroimmunology, and functional genomics approaches in human tissue and animal models to reveal key central-peripheral interactions and to inspire new therapies.

Research

1. Which proteins and immune cells communicate with the brain, and how?

We recently developed cell type-specific and plasma proteome labeling techniques to reveal an unexpected degree and diversity of protein transport across the healthy blood-brain barrier (BBB), reaching neurons, microglia, and other brain cell types.

We are now deciphering the identities, functions, and mechanisms of protein and immune cell signaling across the BBB in health and disease. We seek to understand what distinguishes a protein or immune cell that can enter the brain from those that cannot.

2. How does brain border and immune dysfunction drive neurodegeneration?

We recently generated a first molecular map of the human BBB and choroid plexus. We discovered that brain barrier and immune cells express 30 of the top 45 Alzheimer’s disease (AD) risk genes.

We now seek to understand the role of brain barrier and immune dysfunction in neurodegeneration.

We recently engineered enzymes capable of labeling the proteomes and secretomes of specific cell types to monitor intercellular communication.

We are now developing new tools to deduce the molecular logic of central-peripheral immune interactions and their role in neurodegeneration.

3. What molecular tools can we create to reveal new aspects of brain-body crosstalk?

People

Andrew C. Yang, Principal Investigator

I’m an engineer-turned-neuroscientist developing new molecular approaches to decode the meaning, mechanisms, and therapeutic relevance of protein and immune crosstalk between the brain and body. I joined UCSF as a Sandler Faculty Fellow (2022), and recently started at the Gladstone Institutes & UCSF as an Assistant Professor. I obtained my B.S. in mechanical engineering and materials science at MIT and Ph.D. in bioengineering at Stanford. Outside the lab, I enjoy playing basketball and supporting the LA Lakers and Rams.

Haoyue Zhou, Postdoctoral Scholar

I completed my PhD in Neuroscience from University of Science and Technology of China, where I investigated cerebrovascular disease in the Shen lab. During the process, I became inspired by the studies in the effects of peripheral tissues on the brain through a potential blood-microvessel axis, which formed another idea that I’m interested in. I’m very excited to discover the molecular mechanisms underlying the brain-body communication. Away from my cute cells and mice in lab, I love natural and cultural landscapes.

Yuichi Chayama, Visiting Scientist

I’m a visiting scholar interested in the physiological and pathological mechanisms of molecular and cellular communication between the peripheral cells/tissues and the brain across the blood-brain barrier. I completed my Ph.D. in pharmaceutical sciences at the University of Tokyo, where I investigated adaptive alterations of white adipose tissues prior to and during hibernation in the Syrian hamster. In my free time, I enjoy working out, watching movies, reading books, and going to concerts and live shows.

Madigan Reid, Postdoctoral Scholar

I completed my Ph.D. in Neuroscience at LSU Health Sciences Center in New Orleans where I investigated the protective effect of novel lipid mediators on ischemic stroke, and defined potential molecular targets driving the protection. During my work I became interested in the role of the central and peripheral immune systems in neurological disorders. Outside of the lab I love spending time with friends and family, working out, cooking, and LEGO building.

Maria Kreger Karabova, Postdoctoral Scholar

I have recently completed a PhD programme in Molecular Cell Biology in Health and Disease at the University of Oxford in the UK. My project investigated the role of human microglia in the progression of tau pathology in tauopathies. During my studies, I developed a keen interest in the crosstalk between peripheral and brain-residing immune cells in Alzheimer’s disease. I now hope to explore the molecular mechanisms underlying the crosstalk and how lifestyle modifications may influence such mechanisms in the course of the disease. Away from the bench, you can most likely find me staring down a microscope (EM rocks!), lifting weights, baking, hiking, reading, or drinking way too much coffee.

William Xie, Graduate Student

I am a fourth-year graduate student in the Biomedical Sciences program at UCSF. I performed my undergraduate studies at the University of Cambridge in the UK and was a research associate in Singapore for a year following graduation. I am broadly interested in neuroimmunology, cell engineering, and understanding the rules which govern immune cell trafficking across the blood-brain barrier. Beyond the lab, I enjoy playing my guitar, gymming, and outdoor hikes.

Lexi Schneider, Graduate Student

I’m a fourth-year student in the Biomedical Sciences program and recent transplant from Boston, where I obtained my B.S. in Biological Engineering at MIT. I’m interested in developing molecular tools to better understand the multicellular dynamics underlying neuro and cancer immunology. In my free time, I love playing soccer, listening to music, and exploring the city & surrounding nature with friends.

Xinlan Wen, Graduate Student

I am a third-year student in the Neuroscience program. I obtained my B.S. in Biomedical Science at Shanghai Jiao Tong University, where I studied the neuronal regulation of cerebral blood flow. I am always interested in uncovering the mechanisms of body-brain crosstalks and neuroimmune interactions. In my spare time, I enjoy photographing, dancing, going to concerts and chilling with my cat.

Sophia Nelson, Graduate Student

I’m a third year student in the Biomedical Sciences program. While I’m originally from North Dakota, I got my B.S. at Haverford College in Pennsylvania, where I studied biology with minors in neuroscience and public health. After graduating, I moved cross country to SF and worked as a research technician in Dr. Matthew Krummel’s lab studying cancer immunology. In the Yang Lab, I’m interested in exploring interactions between peripheral immunity and the central nervous system, particularly relating to neuroimmune tolerance in health and disease. Outside of the lab, I love traveling and hiking, tide pooling, making homemade pasta, spoiling my two cats, and hanging out with friends and family.

Janie Oberhauser, Graduate Student

I’m a second-year student in the Neuroscience program. I graduated from the University of North Carolina at Chapel Hill in 2021 with degrees in Biology and English. Afterward, I moved back home to the Bay Area to work as a research associate at Stanford. In the Yang Lab, I’m interested in investigating changes to the blood-brain barrier in aging and neurodegenerative disease. Outside the lab, you can find me reading my way through the leaning tower of books on my nightstand, lamenting the state of the San Jose Sharks, swimming, hiking, and exploring new foods and places.

Andrew Pan, Graduate Student

I’m a second-year student in the Biomedical Sciences program. I grew up in Princeton and then Old Saybrook, a small town in Connecticut. I moved south for college and obtained a B.S in Biomedical Engineering at Georgia Tech doing research in nanoengineering before moving out to San Francisco to work as a research associate at UCSF in Dr. Martin Kampmann’s lab building an in vivo CRISPRi screening platform for the central nervous system. In the Yang lab, I am interested in broadly exploring the role of the blood-brain barrier in Alzheimer’s and how it changes in aging. Outside of lab, I like skiing, tennis, hanging out with my cat, reading, baking, and running.

Runa Cheng, MD/PhD Student

I’m a second-year MSTP and incoming Biological and Medical Informatics program student. I obtained my B.A. in biology at Swarthmore College and minored in chemistry and statistics. After graduation, I joined the Lenardo Lab at the NIH as a postbaccalaureate researcher studying dysregulated immune cell migration to the epithelium in inflammatory bowel disease. In the Yang Lab, I’m interested in investigating changes to the CNS barriers in aging and neurological diseases. Outside the lab, I like to be in nature, explore the city, and play with my cat.

Amanda Coelho Muniz Apolonio, Research Associate

I graduated from UC Berkeley in Molecular Cell Biology with emphasis in Medical Biology and Physiology. Throughout my studies I have developed a great appeal towards the mechanisms that underlines neurological circuits. I have previously joined UCSF through the Department of Physiology in the Scanziani Lab, where I collaborated with determining the network of cortico-fungal neurons responsible for the activation and coordination of visual reflexes. In my free time I enjoy gardening, exploring new spots in the city and catching up with my family.

Fionna Huang, Research Associate

I’m a recent UC Davis alumna with a B.S. in Biochemistry and Molecular Biology. I’ve always been fascinated with human health and disease, and this interest has only grown stronger during my studies. Right now, I’m interested in understanding the underlying mechanisms of diseases to develop new and improved treatments for medical conditions. During my free time, I like to take walks in nature, explore new places, and karaoke.

Bella Ding, Research Associate

I graduated from Macalester College with a B.A. in Applied Math & Statistics and Biology with a biochemistry emphasis. I am intrigued by the intersection of biostatistics and neurodegenerative diseases, hoping to decode the underlying mechanisms behind these complex conditions. In my spare time, I enjoy the simple pleasures of walking and engaging in board games, as well as reading novels.

Mina Negahban, Research Associate

I graduated from UC Davis with a B.S. in Biotechnology. During my time as an undergraduate I worked in the Brown Lab studying neurogenesis within the eye. I am interested in broadening my knowledge of the CNS and how it interacts with the immune system in the Yang Lab. In my free time I enjoy climbing, reading, and baking.

Zimo Zhang, Research Associate

I graduated from Peking University with a B.S. in Life Sciences. Previously I worked in Dr. Yan Song’s lab at Peking University where I studied the development of Drosophila central nervous system. Now, I am interested in mechanisms underlying brain-body interactions, especially in settings of neurological disease. Outside the lab, I enjoy swimming, reading, going to concerts and watching movies.

Alex Pennacchio, Research Associate

I recently completed my undergraduate studies in Biology and Math at Occidental College. Previously, I worked at the Joint Genome Institute where I performed comparative multi-species transcriptomic analysis in plants. My current research interests involve leveraging bioinformatics and machine learning to improve precision health efforts. Outside of work, I enjoy playing golf, cooking Italian food, being in nature, and supporting the LA Chargers.

Sahith Doddipalli, Research Associate

I graduated from UCLA with a B.S. in Biochemistry. My previous work in the Carmichael lab focused on characterizing neural repair responses, such as angiogenesis, in a novel therapeutic hydrogel delivered post-stroke. I’m fascinated by the brain's ability to respond and recover after injury, and I’m excited to investigate how homeostatic dysfunction—particularly in the BBB—can be understood and manipulated for therapeutic intervention. In my free time, I enjoy watching movies and TV shows, exploring new dessert spots, and playing basketball.

Daniela Perla, Research Associate

I graduated from UC Davis with a B.S in Neurobiology, Physiology and Behavior and a minor in Public Health Sciences. Initially, my academic interests were oriented toward osteopathic medicine, drawn by its holistic approach to health and disease. However, my experience in undergraduate research, where I worked on decoding protein-protein interactions between CHD8 and the PAF complex, redirected my interests toward neuroscience and scientific research. I am deeply interested in leveraging the dynamic nature of the immune system and its ability to target specific cellular changes to develop immunotherapies that target specific pathogenic proteins and modulate neuroinflammatory responses. Outside of the lab, I enjoy working out, watching TV shows, going to concerts, exploring new foods and places, and traveling.

Alumni:

Hao Liu, Research Associate 2022-24

Sophie Liu, Research Associate 2022-23

Tamara Utzinger, Master’s Student 2022-23

Publications

 

A first molecular map of the human BBB (Nature, 2022)

Unexpected degree of protein transport across the healthy BBB (Nature, 2020)

Single-cell analysis of neuroinflammation in COVID-19 (Nature, 2021)

The BBB endothelium as a dynamic sensor of peripheral state (Cell Reports, 2020)

Enzymes for cell type-specific bioorthogonal proteome labeling (JACS, 2018)

For a full list of publications, please visit here.

 

Generous funding from

Contact us

We opened our lab in January 2024 at the Gladstone Institutes on the UCSF Mission Bay campus. We’re always excited to talk to and collaborate with those interested in these questions.

1650 Owens Street Gladstone Institutes, 315 San Francisco, CA 94158