About

Dr. Jason T Alexander is an Associate Professor of Medicine in the Department of Medicine at The University of Chicago. He is a clinician educator in the Section of General Internal Medicine and serves as the director of the evidence-based medicine curriculum for the University of Chicago Internal Medicine Residency Program. His research interests include clinical reasoning and data synthesis. Dr. Alexander completed his MD at Emory University in 2012, following a BA in Music and Chemistry from Emory University in 2008. He also completed his residency at the University of Chicago in 2015 and served as Chief Resident at MacNeal Hospital in 2016. His professional focus is on improving internal medicine education and advancing clinical practice through evidence-based approaches.

Research topics

• Biology
• Internal medicine
• Medicine
• Immunology
• Pathology

Selected publications

• Complement at the Nano-Neuroimmune Interface: Implications for Opioid Use Disorder

  Preprints.org · 2026-01-04

  preprintOpen accessSenior author

  The complement system is a central component of innate immunity with established roles in host defense and emerging functions in neurodevelopment, synaptic remodeling, and neuroimmune communication within the central nervous system (CNS). In parallel, advances in nanotechnology have enabled targeted strategies for CNS drug delivery but have also revealed that many nanomaterials interact with and activate complement, influencing biodistribution, safety, and inflammatory responses. Opioid use disorder (OUD) is increasingly recognized as a condition associated with chronic neuroimmune dysregulation involving glial activation, altered cytokine signaling, and blood-brain barrier (BBB) disruption. Although relatively few studies have directly measured complement activation in OUD, emerging transcriptomic, cellular, and inflammatory data suggest that complement pathways may intersect with opioid-induced neuroimmune signaling. This review synthesizes current knowledge at the intersection of complement biology, nanomedicine, and opioid-associated neuroimmune changes. It distinguishes well-established mechanisms of complement activation by nanomaterials from emerging evidence linking complement signaling to opioid exposure. It integrates complement pathways with opioid receptor and Toll-like receptor 4 (TLR4) signaling in glial cells and endothelial compartments, and discusses both beneficial and pathological roles of complement in the CNS. Finally, the therapeutic potential and limitations of complement-aware nanotechnology and complement modulation in CNS drug delivery and addiction neuroscience are outlined to guide translation of complement-targeted nanomedicines in addiction neuroscience.

  PublisherOA PDFDOI

• Complement at the Nano–Neuroimmune Interface: A Hypothesis-Driven Perspective on Opioid Use Disorder

  Immuno · 2026-02-13 · 1 citations

  articleOpen accessSenior author

  The complement system is a central component of innate immunity with established roles in host defense and emerging functions in neurodevelopment, synaptic remodeling, and neuroimmune communication within the central nervous system (CNS). In parallel, advances in nanotechnology have not only enabled targeted strategies for CNS drug delivery but have also revealed that many nanomaterials interact with and activate complement, influencing biodistribution, safety, and inflammatory responses. Opioid use disorder (OUD) is increasingly recognized as a condition associated with chronic neuroimmune dysregulation involving glial activation, altered cytokine signaling, and blood–brain barrier (BBB) disruption. However, direct experimental or clinical measurements of complement activation in OUD remain limited. Current evidence linking complement pathways to opioid exposure is derived largely from indirect observations, including transcriptomic alterations, glial phenotypes, and inflammatory signatures in preclinical and translational models, which collectively suggest, but do not yet definitively establish, complement involvement in opioid-induced neuroimmune signaling. This review synthesizes current knowledge at the intersection of complement biology, nanomedicine, and opioid-associated neuroimmune changes. It distinguishes well-established mechanisms of complement activation by nanomaterials from emerging and inferential evidence linking complement signaling to opioid exposure. This hypothesis-generating framework integrates complement signaling with opioid receptor and TLR4 pathways in glial and endothelial compartments, examining their potential protective and pathological CNS roles while outlining the translational promise and current evidence gaps of complement-aware nanotechnologies for addiction neuroscience.

  PublisherOA PDFDOI

• Gut and oral microbiota characterized in systemic lupus erythematosus patients from India: A pilot study

  Lupus · 2026-03-19

  articleSenior authorCorresponding

  Introduction : Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder influenced both intrinsically by immune cell alterations, genetic factors, and the microbiome, as well as extrinsically by environmental factors. Methods : In this pilot study, we investigated the role of various peripheral immune cells (CD3 + , CD4 + , CD8 + , CD4 + /CD8 + , CD4-/CD8-, NK cells (CD16 + CD56 + ), and CD19 + ) and the gut and salivary microbiota in patients with SLE, comparing these factors to healthy controls. Results and Discussion : Results showed significant alterations in the proportions of CD4 + and CD8 + T cells in SLE patients, with an inverse correlation between these subsets. Additionally, the CD4 + ratio was found to be elevated in SLE. CD4 + T cells were strongly correlated with double-negative T cells, while CD8 + T cells correlated with NK cells. Metagenomic shotgun sequencing of fecal and salivary samples revealed a disruption in the microbiome, particularly the taxa Pasteurellaceae and Veillonella , which were altered in both the gut and oral microbiomes of SLE patients. These changes suggest that there may be overlap in the composition and function of these microbial populations across different body sites. Dysbiosis was observed in both the gut and oral microbiomes of individuals with SLE, distinguishing them from healthy controls. Conclusion : Our findings highlight specific microbiome alterations in SLE patients and suggest that microbiome composition could serve as a potential exploratory tool for diagnosing and prognosticating the disease in larger, adequately powered cohorts.

  PublisherDOI

• Editorial: Women in multiple sclerosis and neuroimmunology: from bench to bedside

  Frontiers in Neurology · 2025-09-30

  editorialOpen access1st authorCorresponding

  Multiple sclerosis (MS) is an inflammatory demyelinating disease with a striking female predominance. The ratio of women:men with MS in some countries has reached 4:1, a trend that has continued to rise over the past few decades 1 . This burgeoning demographic reality highlights the need to understand the biological and clinical aspects of MS and the impact of sex as a variable. This sex disparity, particularly evident in the relapsing/remitting form of MS, mirrors patterns seen in other autoimmune disorders, such as systemic lupus erythematosus, and reflects both biological and epidemiological shifts. The research featured in this special collection brings together the voices and work of women, both as investigators and as subjects of inquiry. Their contributions are reshaping our understanding of MS and other neuroinflammatory conditions, extending from molecular mechanisms to clinical implications. This editorial highlights emerging insights across MS epidemiology, immunobiology, and therapeutic strategy, while reinforcing the critical role of sex-specific research in neurology.A Shifting Epidemiological Landscape: Between 1990 and 2021, global MS incidence rose by nearly 50%, with parallel increases in mortality and disability-adjusted life years (DALYs) 2 . Population growth, aging, and improved diagnostics such as the widespread availability of MRI and updated diagnostic criteria are suggested as major contributors to this rise. Developed countries report the highest MS burden, led by USA in incident cases 1 . Availability of disease modifying therapies have transformed the disease course with reduced relapse rates and slower progression. Environmental and lifestyle risk factors including Epstein-Barr virus infection, vitamin D deficiency, smoking and early life obesity, their interaction with genetics and disturbed homeostasis continue to shape the global prevalence of MS.Sex differences in MS extend beyond prevalence to fundamental immune mechanisms. In the study by Laaksonen et al., positron emission tomography revealed higher translocator protein (TSPO) binding, reflecting activated microglia/macrophages and astrocytes, in men compared to women with MS and even among healthy controls. Their results suggests that central nervous system (CNS) cells may differ phenotypically and functionally between the sexes in MS and men may harbor a lower neuroinflammatory threshold that predisposes them to more aggressive neurodegeneration. Animal studies echo these findings, showing male microglia to be more pro-inflammatory, while female microglia may promote neuroprotection and repair 3 . Estrogen likely contributes to this protective effect, although its precise role remains under investigation. Understanding these immunological dimorphisms is essential, especially as we move toward tailored interventions targeting cell function.The complement system, an important arm of the innate immune system, is increasingly recognized as a central player in neurodegeneration. In their review, Negro-Demontel et al. explore the dual role of complement components in the brain: facilitating development and synaptic pruning under physiological conditions, while also driving pathology in diseases such as MS, Alzheimer's (AD), Parkinson's (PD), and Huntington's (HD). In MS, complement deposition (C1q, C3) and membrane attack complex (MAC) formation are found in active lesions, correlating with disease activity. In AD, complement overactivation has been implicated in synaptic loss. The review also introduces the concept of the intracellular complement "complosome" and its emerging relevance to CNS disease, as well as the hypothesized link between persistent viral infections (e.g., EBV, HHV-6) and complement-mediated neurodegeneration. These insights point toward a future where complement-targeted therapies could be tailored not only by disease but also by sex, aging, and cell type.Aging and Immunosenescence: While Disease-Modifying Therapies have revolutionized MS care, their safety and efficacy profiles in older adults remain underexplored. Sabin Muñoz et al. present a compelling case of a 63-year-old woman with late-onset MS who developed primary cytomegalovirus (CMV) infection while on dimethyl fumarate (DMF), despite no documented lymphopenia. Immunosenescence, the natural decline in immune function with age, may alter both therapeutic responses and susceptibility to opportunistic infections, demanding a nuanced, individualized approach to treatment selection in older patients. This case highlights the critical need for age-inclusive research, as adverse events related to aging and immunosenescence are likely to be underreported in clinical trials that predominately enroll younger individuals or enforce age-based enrollment restrictions.Identifying reliable biomarkers for MS subtypes remains a critical frontier. Dessu et al. reviewed the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) levels across MS phenotypes. Although NfL serves as a reliable marker of axonal damage and correlates with disease activity, the authors demonstrate NfL cannot clearly differentiate between relapsing-remitting MS (RRMS) and progressive MS subtypes, restricting its value as a biomarker for disease progression. The field may benefit from integrating multiple biomarker modalities, including fluid biomarker panels (e.g. tissue injury and inflammatory markers), neuroimaging, and clinical indicators. Longitudinal, multi-modal assessments could yield more accurate predictors of progression and therapeutic response.Broader Implications of Sex in Neurodegeneration, Beyond MS: Sex differences are not confined to MS. In Huntington's disease (HD), although genetic penetrance is equal across sexes, women often experience more severe progression and heightened psychiatric burden, particularly depression. As Risby-Jones et al. report, female glial cells, including microglia, astrocytes, and oligodendrocytes, demonstrate heightened inflammatory responses and impaired repair capacity. These findings raise the possibility that glial-targeted therapies might require sex-specific calibration. For example, female astrocytes show higher GFAP expression and reduced phagocytic activity, while female oligodendrocytes may struggle with differentiation and remyelination. Therapeutic strategies that support glial resilience may therefore benefit from tailored design based on sex-specific cellular responses.Looking Ahead: From Inclusivity to Personalized Precision: This collection of studies affirms that sex is a critical lens through which all neuroimmunology research must be examined. MS and other autoimmune diseases serve as compelling examples, given their female predominance, immunological complexity, and clinical heterogeneity, and provide an ideal model system for integrating sex-focused approaches into both research and care. This issue also advocates for the critical need for diversity, not only in study populations, but also in scientific leadership. The strong presence of female scientists in this issue and their collective work embodies the translational ethos to bridge the gap from bench to bedside. Future research must therefore continue to champion integrative strategies that incorporate age, sex, immune profile, and neurobiology. Through such dedicated efforts, precision neurology can become more than a goal, it can become the standard.

  PublisherOA PDFDOI

• Neuroinflammation links the neurogenic and neurodegenerative phenotypes of <i> Nrmt1 ^-/- </i> mice

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-07

  preprintOpen access

  Abstract It is widely thought that age-related damage is the single biggest contributing factor to neurodegenerative diseases. However, recent studies are beginning to indicate that many of these diseases may have developmental origins that become unmasked overtime. It has been difficult to prove these developmental origins, as there are still few known links between defective embryonic neurogenesis and progressive neurodegeneration. We have created a constitutive knockout mouse for the N-terminal methyltransferase NRMT1 ( Nrmt1 -/- mice). Nrmt1 -/- mice display phenotypes associated with premature aging. Specifically in the brain, they exhibit age-related striatal and hippocampal degeneration, which is accompanied by impaired short and long-term memory. These phenotypes are preceded by depletion of the postnatal neural stem cell (NSC) pools, which appears to be driven by their premature differentiation and migration. However, this differentiation is often incomplete, as many resulting neurons cannot permanently exit the cell cycle and ultimately undergo apoptosis. Here, we show that the onset of apoptosis corresponds to increased cleavage of p35 into the CDK5 activator p25, which can promote neuroinflammation. Accordingly, Nrmt1 -/- brains exhibit an increase in pro-inflammatory cytokine signaling, astrogliosis, complement activation, microgliosis, and markers of a compromised blood brain barrier, all of which indicate an activated neuroimmune response. We also find Nrmt1 -/- mice do not activate a corresponding anti-inflammatory response. These data indicate that abnormal neurogenesis can trigger neuroinflammation, which in the absence of compensatory anti-inflammatory signaling, could lead to neuronal apoptosis and progressive neurodegeneration.

  PublisherOA PDFDOI

• Intrinsic macrophage factor H plays a critical role in kidney homeostasis 4162

  The Journal of Immunology · 2025-11-01

  articleOpen access1st authorCorresponding

  Abstract Description The complement cascade is a key component of the innate immune system. Dysfunction of the complement regulator, factor H (FH) is linked to kidney disease, often accompanied by macrophage infiltration. Hepatic FH regulates serum complement activation, while intrinsic FH in cells such as macrophages regulates complement activation and maintains local homeostasis. Macrophages are heterogeneous and influenced by their microenvironment, prompting us to investigate the role of macrophage-derived FH in kidney pathology and fibrosis. We generated FloxFH (FHfl/fl) mice and crossed them with CMVcre, CX3CR1cre, and Csfr1cre mice to produce conditional FH knockout (cKO) mice with no FH (FHfl/flCMVcre) and with FH absent in the macrophages (FHfl/flCX3CR1cre and FHfl/flCsfr1cre). The mice were treated with horse spleen apoferritin to induce chronic serum sickness. FHfl/flCMVcre mice exhibited a significant increase in immune complexes in the glomeruli compared to FHfl/fl controls. FHfl/flCX3CR1cre and FHfl/flCsfr1cre mice showed kidney dysfunction and immune deposits, with FHfl/flCX3CR1cre deposits resembling those seen in global FH knockouts. Additionally, TGF-β and laminin expression were significantly elevated in the kidneys of the cKO mice. Our results for the first time, highlight the critical role of macrophage-derived FH in limiting inflammation, preventing kidney pathology, as well as its involvement in the development of fibrosis in immune complex-mediated kidney disease. Funding Sources N/A Topic Categories Immune Mechanisms of Human Disease (HUM)

  PublisherOA PDFDOI

• The complement system and kidney cancer: pathogenesis to clinical applications

  Journal of Clinical Investigation · 2025-05-01 · 6 citations

  reviewOpen accessSenior author

  Kidney cancer poses unique clinical challenges because of its resistance to conventional treatments and its tendency to metastasize. The kidney is particularly susceptible to dysfunction of the complement system, an immune network that tumors often exploit. Recent discoveries have highlighted that the complement system not only plays a crucial role in immune surveillance and defense in the circulatory system, but also functions intracellularly and autonomously. This concept has shifted the focus of investigation toward understanding how complement proteins influence cancer progression by regulating the tumor microenvironment (TME), cell signaling, proliferation, metabolism, and the immune response. With the complement system and its inhibitors emerging as a promising new class of immunotherapeutics and potential complement-targeted treatments advancing through development pipelines and clinical trials, this Review provides a timely examination of how harnessing the complement system could lead to effective tumor treatments and how to strategically combine complement inhibitors with other cancer treatments, offering renewed hope in the fight against kidney cancer.

  PublisherOA PDFDOI

• Macrophage-derived complement factor H restrains kidney inflammation and fibrosis in immune complex-mediated disease

  Immunobiology · 2025-07-01 · 1 citations

  articleOpen access1st authorCorresponding

  Complement factor H (FH) is a key regulator of the alternative pathway, limiting complement activation by negatively controlling C3 consumption. Deficiency or dysfunction of FH is strongly associated with kidney disease, where monocytes and macrophages are critical contributors. Notably, FH is expressed by these myeloid cells and regulates cell-intrinsic complement activity to maintain local immune homeostasis. Given the heterogeneity of macrophages and their context-dependent roles, we investigated the specific contribution of macrophage-derived FH in kidney pathology and fibrosis. We generated FloxFH (FHfl/fl) mice and bred them with CMVcre, CX3CR1cre, and Csfr1cre strains to produce conditional FH knockout (cFHKO) mice: systemic FH deficiency (FHfl/flCMVcre), and macrophage-specific FH deletion (FHfl/flCX3CR1cre and FHfl/flCsfr1cre). Mice were subjected to chronic serum sickness (CSS) using horse spleen apoferritin to induce immune complex-mediated kidney injury. FHfl/flCMVcre mice displayed significant glomerular immune complex deposition compared to controls. Strikingly, macrophage-specific cFHKO mice (FHfl/fCX3CR1cre and FHfl/flCsfr1cre) developed kidney dysfunction and immune complex accumulation, with FHfl/flCX3CR1cre mice recapitulating features seen in global FH deficiency. Furthermore, elevated renal expression of TGF-β and laminin indicated enhanced fibrotic responses. These findings establish, for the first time, that macrophage-derived FH plays a pivotal role in modulating complement activation, controlling inflammation, and preventing fibrosis in immune complex-driven kidney disease.

  PublisherDOI

• Melatonin as a potential adjunct therapy for central nervous system lupus: evidence from the MRL/lpr mouse model

  Precision Clinical Medicine · 2024-09-30

  articleOpen accessSenior author
  PublisherDOI

• Metabolic changes during evolution of Sjögren's in both an animal model and human patients

  Heliyon · 2024-12-11 · 1 citations

  articleOpen access

  mice at 10-12 months of age. Additional studies are suggested to further define metabolic activities at the various disease stages.

  PublisherDOI

Recent grants

• Mechanisms of Complement Dependent Immune Complex-Mediated Glomerulonephritis

  NIH · $712k · 2018–2021

Frequent coauthors

• Brigitte M. Lobnig

  495 shared

• Stefan Kölker

  Heidelberg University

  338 shared

• Hugo Ten Cate

  Maastricht University

  332 shared

• Masaomi Nangaku

  The University of Tokyo

  332 shared

• Andrew L. Wong

  329 shared

• Hideki Kato

  Tohoku University

  318 shared

• Alexander K. C. Leung

  181 shared

• Ronnie Fass

  Case Western Reserve University

  169 shared

Labs

• University of Chicago Department of Medicine-General Internal MedicinePI

Education

• B.A., Music and Chemistry

  Emory University

  2008

• M.D.

  Emory University

  2012

• Other

  University of Chicago

  2015

• Other

  MacNeal Hospital

  2016