Bio


Sai Folmsbee is a clinical assistant professor in the neuropsychiatry section and leads the Neuroimmunology Disorders Neuropsychiatry Clinic. He is also a member of the Stanford Autoimmune Encephalitis Clinic (AEC), focusing on the treatment of the psychiatric symptoms of immune-mediated epilepsy/encephalitis. His clinical and research interests include the psychiatric manifestations and treatment of immune-mediated illness. He graduated from the Medical Scientist Training Program at Northwestern Feinberg School of Medicine, where he received his Ph.D. investigating the role of cell adhesion in immunologic and neurologic processes. He completed his general psychiatry residency training in the Psychiatry Research Pathway at the University of Pittsburgh. Afterwards, he completed the Neuropsychiatry and Behavioral Neurology Fellowship at Stanford University and joined the faculty in 2023. Currently, he is also the Neuropsychiatry Fellowship Course Director and Neuropsychiatry Rotation Director, as well as a faculty mentor for the Stanford Comprehensive Neurology Instructorship.

Clinical Focus


  • Psychiatry
  • Neuropsychiatry
  • Neuroimmunology

Academic Appointments


Honors & Awards


  • Innovator Grant, Stanford University Department of Psychiatry and Behavioral Sciences (2023)
  • Trailblazing Trainee Award, Stanford University Department of Psychiatry and Behavioral Sciences (2023)
  • Gold Foundation Humanism and Excellence in Teaching Award, University of Pittsburgh Medical School (2019)
  • Professionalism Accolade, University of Pittsburgh Medical School (2018, 2019)
  • Stephen M. Stahl Award for Excellence in Psychiatry, Northwestern University Feinberg School of Medicine (2018)
  • F30 National Research Service Award Individual Fellowship, Northwestern Feinberg School of Medicine (2015-2017)

Professional Education


  • Fellowship: Stanford University Psychiatry and Behavioral Sciences (2023) CA
  • Board Certification: American Board of Psychiatry, Psychiatry (2022)
  • Residency: University of Pittsburgh Medical Center Psychiatry Program (2022) PA
  • Medical Education: Northwestern University Feinberg School of Medicine (2018) IL

Current Research and Scholarly Interests


My current research interest is the intersection of psychiatry and neuroimmunology. I am currently collaborating with Stanford Neuroimmunology in a retrospective analysis of patient data to determine the relationship between psychaitric medications and clinical outcomes in hospitalized patients with mutliple sclerosis, autoimmune encephalitis, and neuromyelitis optica.

All Publications


  • Antipsychotic medications associated with increased length of hospital stay in autoimmune encephalitis and multiple sclerosis: A retrospective study. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Sai Folmsbee, S., Hui, G., Yuan, Y., Gombar, S., Han, M., Le, S. 2024; 124: 87-93

    Abstract

    Antipsychotic medications (APMs) and selective serotonin reuptake inhibitors (SSRIs) are frequently utilized in patients with neuroinflammatory disorders, such as autoimmune encephalitis and multiple sclerosis (MS). This retrospective study investigates how in-hospital treatment with APMs and SSRIs in patients with these neuroinflammatory diseases are associated with differences in hospital length-of-stay (LOS) and mortality.We evaluated all the inpatients in the Stanford University Hospital from 2008 to 2023 diagnosed with either non-infectious encephalitis or MS and subdivided them into those who did or did not receive APMs or SSRIs while hospitalized. We then analyzed whether hospital LOS and mortality differed with these medications.Among inpatients with non-infectious encephalitis (n = 114), those who were exposed to APMs had a significantly increased mean LOS (11.8 vs 20.9 days, p < 0.01). For inpatients with MS (n = 1095), treatment with an APM was associated with a significant increase in mean LOS (2.8 vs. 7.1, p < 0.00001). When comparing typical to atypical APMs given to subjects with MS, those who received atypical APMs showed a significant increase in LOS (4.3 vs 10.5, p < 0.01), although typical APMs showed significantly increased risk of mortality (p < 0.05). For inpatients with MS and SSRI use, there was a significant increase in mean hospital LOS (3.5 vs 5.3, p < 0.01), with a significant difference found in those who received fluoxetine or citalopram, but not sertraline or escitalopram. Finally, several healthcare disparities were found, including that Black patients were more likely to receive APMs, and those with MS were more likely to receive typical rather than atypical APMs. Conversely, Black patients with MS were less likely to receive SSRI treatment.There was a statistically significant increase in LOS associated with APM use in non-infectious encephalitis and MS, as well as with SSRI use in MS. These data reflect the importance of these medications in these neuroinflammatory disorders and suggest that further investigation into their risks and benefits would be warranted.

    View details for DOI 10.1016/j.jocn.2024.04.021

    View details for PubMedID 38677201

  • Investigating the Use of Virtual Reality Technology for Psychiatric Neuroimaging Education. Academic psychiatry : the journal of the American Association of Directors of Psychiatric Residency Training and the Association for Academic Psychiatry Folmsbee, S. S., Medina, M., Tran, H., Nguyen, P., Bajestan, S. 2024

    View details for DOI 10.1007/s40596-024-01937-3

    View details for PubMedID 38291314

    View details for PubMedCentralID 10080019

  • Cardiomyocytes of the Heart and Pulmonary Veins: Novel Contributors to Asthma? American journal of respiratory cell and molecular biology Folmsbee, S. S., Gottardi, C. J. 2017; 57 (5): 512-518

    Abstract

    Recent genome-wide association studies have implicated both cardiac and pulmonary vein-related genes in the pathogenesis of asthma. Since cardiac cells are not present in lung airways or viewed to affect the immune system, interpretation of these findings in the context of more well-established contributors to asthma has remained challenging. However, cardiomyocytes are present in the lung, specifically along pulmonary veins, and recent murine models suggest that cardiac cells lining the pulmonary veins may contribute to allergic airway disease. Notably, the cardiac cell-junction protein αT-catenin (αT-cat, CTNNA3), which is implicated in occupational and steroid-resistant asthma by clinical genetic data, appears to play an important role in regulating inflammation around the cardiac cells of pulmonary veins. Beyond the potential contribution of pulmonary veins, clinical data directly examining cardiac function through echocardiography have found strong associations between asthmatic phenotypes and the mechanical properties of the heart. Together, these data suggest that targeting the function of cardiac cells in the pulmonary veins and/or heart may allow for novel and potentially efficacious therapies for asthma, particularly in challenging cases of steroid-resistant asthma.

    View details for DOI 10.1165/rcmb.2016-0261TR

    View details for PubMedID 28481622

    View details for PubMedCentralID PMC5705903

  • The cardiomyocyte protein αT-catenin contributes to asthma through regulating pulmonary vein inflammation. The Journal of allergy and clinical immunology Folmsbee, S. S., Budinger, G. R., Bryce, P. J., Gottardi, C. J. 2016; 138 (1): 123-129.e2

    Abstract

    Recent genome-wide association studies have identified single nucleotide polymorphisms in the gene encoding the protein αT-catenin (CTNNA3) that correlate with both steroid-resistant atopic asthma and asthmatic exacerbations. α-Catenins are important mediators of cell-cell adhesion, and αT-catenin is predominantly expressed in cardiomyocytes. In the lung αT-catenin appears to be exclusively expressed in cardiomyocytes surrounding the pulmonary veins (PVs), but its contribution to atopic asthma remains unknown.We sought to understand the role of αT-catenin in asthma pathogenesis.We used αT-catenin knockout mice and a house dust mite (HDM) extract model of atopic asthma, with assessment by means of forced oscillation, bronchoalveolar lavage, and histologic analysis.We found that the genetic loss of αT-catenin in mice largely attenuated HDM-induced airway inflammation and airway hyperresponsiveness to methacholine. Mice lacking αT-catenin that were exposed to HDM extract had reduced PV inflammation, specifically near the large veins surrounded by cardiac cells. The proximity of the airways to PVs correlated with the severity of airway goblet cell metaplasia, suggesting that PVs can influence the inflammatory milieu of adjacent airways. Loss of αT-catenin led to compensatory upregulation of αE-catenin, which itself has a defined anti-inflammatory function.These data mechanistically support previous clinical and genetic associations between αT-catenin and the development of atopic asthma and suggest that PVs might have an underappreciated role in allergic airway inflammation.

    View details for DOI 10.1016/j.jaci.2015.11.037

    View details for PubMedID 26947180

    View details for PubMedCentralID PMC4931945

  • αT-catenin in restricted brain cell types and its potential connection to autism. Journal of molecular psychiatry Folmsbee, S. S., Wilcox, D. R., Tyberghein, K., De Bleser, P., Tourtellotte, W. G., van Hengel, J., van Roy, F., Gottardi, C. J. 2016; 4: 2

    Abstract

    Recent genetic association studies have linked the cadherin-based adherens junction protein alpha-T-catenin (αT-cat, CTNNA3) with the development of autism. Where αT-cat is expressed in the brain, and how its loss could contribute to this disorder, are entirely unknown.We used the αT-cat knockout mouse to examine the localization of αT-cat in the brain, and we used histology and immunofluorescence analysis to examine the neurobiological consequences of its loss.We found that αT-cat comprises the ependymal cell junctions of the ventricles of the brain, and its loss led to compensatory upregulation of αE-cat expression. Notably, αT-cat was not detected within the choroid plexus, which relies on cell junction components common to typical epithelial cells. While αT-cat was not detected in neurons of the cerebral cortex, it was abundantly detected within neuronal structures of the molecular layer of the cerebellum. Although αT-cat loss led to no overt differences in cerebral or cerebellar structure, RNA-sequencing analysis from wild type versus knockout cerebella identified a number of disease-relevant signaling pathways associated with αT-cat loss, such as GABA-A receptor activation.These findings raise the possibility that the genetic associations between αT-cat and autism may be due to ependymal and cerebellar defects, and highlight the potential importance of a seemingly redundant adherens junction component to a neurological disorder.

    View details for DOI 10.1186/s40303-016-0017-9

    View details for PubMedID 27330745

    View details for PubMedCentralID PMC4915096

  • The Type I Interferon Response Determines Differences in Choroid Plexus Susceptibility between Newborns and Adults in Herpes Simplex Virus Encephalitis. mBio Wilcox, D. R., Folmsbee, S. S., Muller, W. J., Longnecker, R. 2016; 7 (2): e00437-16

    Abstract

    Newborns are significantly more susceptible to severe viral encephalitis than adults, with differences in the host response to infection implicated as a major factor. However, the specific host signaling pathways responsible for differences in susceptibility and neurologic morbidity have remained unknown. In a murine model of HSV encephalitis, we demonstrated that the choroid plexus (CP) is susceptible to herpes simplex virus 1 (HSV-1) early in infection of the newborn but not the adult brain. We confirmed susceptibility of the CP to HSV infection in a human case of newborn HSV encephalitis. We investigated components of the type I interferon (IFN) response in the murine brain that might account for differences in cell susceptibility and found that newborns have a dampened interferon response and significantly lower basal levels of the alpha/beta interferon (IFN-α/β) receptor (IFNAR) than do adults. To test the contribution of IFNAR to restricting infection from the CP, we infected IFNAR knockout (KO) adult mice, which showed restored CP susceptibility to HSV-1 infection in the adult. Furthermore, reduced IFNAR levels did not account for differences we found in the basal levels of several other innate signaling proteins in the wild-type newborn and the adult, including protein kinase R (PKR), that suggested specific regulation of innate immunity in the developing brain. Viral targeting of the CP, a region of the brain that plays a critical role in neurodevelopment, provides a link between newborn susceptibility to HSV and long-term neurologic morbidity among survivors of newborn HSV encephalitis.Compared to adults, newborns are significantly more susceptible to severe disease following HSV infection. Over half of newborn HSV infections result in disseminated disease or encephalitis, with long-term neurologic morbidity in 2/3 of encephalitis survivors. We investigated differences in host cell susceptibility between newborns and adults that contribute to severe central nervous system disease in the newborn. We found that, unlike the adult brain, the newborn choroid plexus (CP) was susceptible early in HSV-1 infection. We demonstrated that IFN-α/β receptor levels are lower in the newborn brain than in the adult brain and that deletion of this receptor restores susceptibility of the CP in the adult brain. The CP serves as a barrier between the blood and the cerebrospinal fluid and plays a role in proper neurodevelopment. Susceptibility of the newborn choroid plexus to HSV-1 has important implications in viral spread to the brain and, also, in the neurologic morbidity following HSV encephalitis.

    View details for DOI 10.1128/mBio.00437-16

    View details for PubMedID 27073094

    View details for PubMedCentralID PMC4959527

  • α-Catenin phosphorylation promotes intercellular adhesion through a dual-kinase mechanism. Journal of cell science Escobar, D. J., Desai, R., Ishiyama, N., Folmsbee, S. S., Novak, M. N., Flozak, A. S., Daugherty, R. L., Mo, R., Nanavati, D., Sarpal, R., Leckband, D., Ikura, M., Tepass, U., Gottardi, C. J. 2015; 128 (6): 1150-65

    Abstract

    The cadherin-catenin adhesion complex is a key contributor to epithelial tissue stability and dynamic cell movements during development and tissue renewal. How this complex is regulated to accomplish these functions is not fully understood. We identified several phosphorylation sites in mammalian αE-catenin (also known as catenin α-1) and Drosophila α-Catenin within a flexible linker located between the middle (M)-region and the carboxy-terminal actin-binding domain. We show that this phospho-linker (P-linker) is the main phosphorylated region of α-catenin in cells and is sequentially modified at casein kinase 2 and 1 consensus sites. In Drosophila, the P-linker is required for normal α-catenin function during development and collective cell migration, although no obvious defects were found in cadherin-catenin complex assembly or adherens junction formation. In mammalian cells, non-phosphorylatable forms of α-catenin showed defects in intercellular adhesion using a mechanical dispersion assay. Epithelial sheets expressing phosphomimetic forms of α-catenin showed faster and more coordinated migrations after scratch wounding. These findings suggest that phosphorylation and dephosphorylation of the α-catenin P-linker are required for normal cadherin-catenin complex function in Drosophila and mammalian cells.

    View details for DOI 10.1242/jcs.163824

    View details for PubMedID 25653389

    View details for PubMedCentralID PMC4359922

  • The cardiac protein αT-catenin contributes to chemical-induced asthma. American journal of physiology. Lung cellular and molecular physiology Folmsbee, S. S., Morales-Nebreda, L., Van Hengel, J., Tyberghein, K., Van Roy, F., Budinger, G. R., Bryce, P. J., Gottardi, C. J. 2015; 308 (3): L253-8

    Abstract

    Ten to 25% of adult asthma is occupational induced, a subtype caused by exposure to workplace chemicals. A recent genomewide association study identified single-nucleotide polymorphisms in the cardiac protein αT-catenin (αT-cat) that correlated with the incidence and severity of toluene diisocyanate (TDI) occupational asthma. αT-cat is a critical mediator of cell-cell adhesion and is predominantly expressed in cardiomyocytes, but its connection to asthma remains unknown. Therefore, we sought to determine the primary αT-cat-expressing cell type in the lung and its contribution to lung physiology in a murine model of TDI asthma. We show that αT-cat is expressed in lung within the cardiac sheath of pulmonary veins. Mechanically ventilated αT-cat knockout (KO) mice exhibit a significantly increased pressure-volume curve area compared with wild-type (WT) mice, suggesting that αT-cat loss affects lung hysteresis. Using a murine model of TDI asthma, we find that αT-cat KO mice show increased airway hyperresponsiveness to methacholine compared with WT mice. Bronchoalveolar lavage reveals only a mild macrophage-dominant inflammation that is not significantly different between WT and KO mice. These data suggest that αT-cat may contribute to asthma through a mechanism independent of inflammation and related to heart and pulmonary vein dysfunction.

    View details for DOI 10.1152/ajplung.00331.2014

    View details for PubMedID 25480337

    View details for PubMedCentralID PMC4340121

  • Ewing sarcoma EWS protein regulates midzone formation by recruiting Aurora B kinase to the midzone. Cell cycle (Georgetown, Tex.) Park, H., Turkalo, T. K., Nelson, K., Folmsbee, S. S., Robb, C., Roper, B., Azuma, M. 2014; 13 (15): 2391-9

    Abstract

    Ewing sarcoma is a malignant bone cancer that primarily occurs in children and adolescents. Eighty-five percent of Ewing sarcoma is characterized by the presence of the aberrant chimeric EWS/FLI1 fusion gene. Previously, we demonstrated that an interaction between EWS/FLI1 and wild-type EWS led to the inhibition of EWS activity and mitotic dysfunction. Although defective mitosis is considered to be a critical step in cancer initiation, it is unknown how interference with EWS contributes to Ewing sarcoma formation. Here, we demonstrate that EWS/FLI1- and EWS-knockdown cells display a high incidence of defects in the midzone, a midline structure located between segregating chromatids during anaphase. Defects in the midzone can lead to the failure of cytokinesis and can result in the induction of aneuploidy. The similarity among the phenotypes of EWS/FLI1- and EWS siRNA-transfected HeLa cells points to the inhibition of EWS as the key mechanism for the induction of midzone defects. Supporting this observation, the ectopic expression of EWS rescues the high incidence of midzone defects observed in Ewing sarcoma A673 cells. We discovered that EWS interacts with Aurora B kinase, and that EWS is also required for recruiting Aurora B to the midzone. A domain analysis revealed that the R565 in the RGG3 domain of EWS is essential for both Aurora B interaction and the recruitment of Aurora B to the midzone. Here, we propose that the impairment of EWS-dependent midzone formation via the recruitment of Aurora B is a potential mechanism of Ewing sarcoma development.

    View details for DOI 10.4161/cc.29337

    View details for PubMedID 25483190

    View details for PubMedCentralID PMC4128884