Serena Spudich, MD, MA
Research & Publications
Biography
News
Research Summary
Our group’s clinical and translational research focuses on characterization of the central nervous system in humans with HIV and other infections. Our long-term goal is to understand and develop effective treatments for neurological complications of infectious diseases. Our particular interest is in the early establishment of central nervous system inflammation and injury in the nervous system in acute infection, and how this relates to ongoing neurologic damage, persistent infection within the central nervous system, and enduring neurological impairment in people with HIV and other infections.
Our current program employs a multidisciplinary approach to patient-oriented research in neuroHIV and other infectious diseases through fruitful collaborations with researchers in immunology, radiology, neuropsychology, virology, and molecular biomarkers. Our studies focus on study participants who can reveal unique facets of neuropathogenesis of viral infections, including individuals with acute or early HIV infection, patients at different stages of treatment with antiretroviral therapy, and individuals with cerebrospinal fluid HIV escape (detected HIV in the central nervous system despite effective treatment in the blood). We also perform clinical studies aimed to reduce early establishment of central nervous system reservoirs for HIV infection, and studies interrogating the cellular landscape of brain tissue from donors with HIV and substance use disorders. Since 2020, we have applied tools that we have developed over the past 20 years in studies of HIV neuropathogesis to systematic studies of the biological processes underlying neurologic symptoms persisting post-acute COVID-19.
We study participants recruited at urban centers in the US and international sites including Bangkok, Thailand. Broader involvement with the design and implementation of multicenter studies relevant to neurological infections is facilitated by Dr. Spudich’s positions within the international AIDS Clinical Trials Group (ACTG) through an affiliation with the Cornell AIDS Clinical Trials Unit, and as CoPI of the NIH/NINDS-funded Yale NeuroNEXT clinical site.
Specialized Terms: HIV; AIDS; Central nervous system inflammation; Viral compartmentalization; Acute infection; HIV reservoirs; Magnetic resonance spectroscopy; Diffusion tensor imaging; Neural markers; Cerebrospinal fluid biomarkers
Coauthors
Research Interests
Acquired Immunodeficiency Syndrome; Antiviral Agents; Cerebrospinal Fluid; Dementia; HIV; Nervous System; Neurology; Virology; Positron-Emission Tomography; Biomarkers, Pharmacological; COVID-19
Public Health Interests
Aging; Biomarkers; Disease Transmission; HIV/AIDS; Immunology; Infectious Diseases; Viruses
Selected Publications
- Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review.Zubair AS, McAlpine LS, Gardin T, Farhadian S, Kuruvilla DE, Spudich S. Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review. JAMA Neurology 2020, 77: 1018-1027. PMID: 32469387, PMCID: PMC7484225, DOI: 10.1001/jamaneurol.2020.2065.
- Central Nervous System Safety During Brief Analytic Treatment Interruption of Antiretroviral Therapy Within 4 Human Immunodeficiency Virus Remission Trials: An Observational Study in Acutely Treated People Living With Human Immunodeficiency Virus.Hellmuth J, Muccini C, Colby DJ, Kroon E, de Souza M, Crowell TA, Chan P, Sacdalan C, Intasan J, Benjapornpong K, Tipsuk S, Puttamaswin S, Chomchey N, Valcour V, Sarnecki M, Tomaka F, Krebs SJ, Slike BM, Jagodzinski LL, Dumrongpisutikul N, Sailasuta N, Samboju V, Michael NL, Robb ML, Vasan S, Ananworanich J, Phanuphak P, Phanuphak N, Paul R, Spudich S. Central Nervous System Safety During Brief Analytic Treatment Interruption of Antiretroviral Therapy Within 4 Human Immunodeficiency Virus Remission Trials: An Observational Study in Acutely Treated People Living With Human Immunodeficiency Virus. Clinical Infectious Diseases : An Official Publication Of The Infectious Diseases Society Of America 2021, 73: e1885-e1892. PMID: 32916708, PMCID: PMC8492357, DOI: 10.1093/cid/ciaa1344.
- Lessons from a neurology consult service for patients with COVID-19.McAlpine LS, Zubair AS, Moeller J, Baehring J, Spudich S. Lessons from a neurology consult service for patients with COVID-19. The Lancet. Neurology 2020, 19: 806-807. PMID: 32949536, PMCID: PMC7494315, DOI: 10.1016/S1474-4422(20)30316-1.
- Very Early Initiation of Antiretroviral Therapy During Acute HIV Infection Is Associated With Normalized Levels of Immune Activation Markers in Cerebrospinal Fluid but Not in Plasma.Hellmuth J, Slike BM, Sacdalan C, Best J, Kroon E, Phanuphak N, Fletcher JLK, Prueksakaew P, Jagodzinski LL, Valcour V, Robb M, Ananworanich J, Allen IE, Krebs SJ, Spudich S. Very Early Initiation of Antiretroviral Therapy During Acute HIV Infection Is Associated With Normalized Levels of Immune Activation Markers in Cerebrospinal Fluid but Not in Plasma. The Journal Of Infectious Diseases 2019, 220: 1885-1891. PMID: 30668739, PMCID: PMC6833977, DOI: 10.1093/infdis/jiz030.
- Persistent HIV-infected cells in cerebrospinal fluid are associated with poorer neurocognitive performance.Spudich S, Robertson KR, Bosch RJ, Gandhi RT, Cyktor JC, Mar H, Macatangay BJ, Lalama CM, Rinaldo C, Collier AC, Godfrey C, Eron JJ, McMahon D, Jacobs JL, Koontz D, Hogg E, Vecchio A, Mellors JW. Persistent HIV-infected cells in cerebrospinal fluid are associated with poorer neurocognitive performance. The Journal Of Clinical Investigation 2019, 129: 3339-3346. PMID: 31305262, PMCID: PMC6668666, DOI: 10.1172/JCI127413.
- Potential for early antiretroviral therapy to reduce central nervous system HIV-1 persistence.Spudich S, Peterson J, Fuchs D, Price RW, Gisslen M. Potential for early antiretroviral therapy to reduce central nervous system HIV-1 persistence. AIDS (London, England) 2019, 33 Suppl 2: S135-S144. PMID: 31789814, DOI: 10.1097/QAD.0000000000002326.
- Anti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir?Burbelo PD, Price RW, Hagberg L, Hatano H, Spudich S, Deeks SG, Gisslén M. Anti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir? The Journal Of Infectious Diseases 2018, 217: 1024-1032. PMID: 29401308, PMCID: PMC5939835, DOI: 10.1093/infdis/jix662.
- Longitudinal Trajectories of Brain Volume and Cortical Thickness in Treated and Untreated Primary Human Immunodeficiency Virus Infection.Sanford R, Ances BM, Meyerhoff DJ, Price RW, Fuchs D, Zetterberg H, Spudich S, Collins DL. Longitudinal Trajectories of Brain Volume and Cortical Thickness in Treated and Untreated Primary Human Immunodeficiency Virus Infection. Clinical Infectious Diseases : An Official Publication Of The Infectious Diseases Society Of America 2018, 67: 1697-1704. PMID: 29697762, PMCID: PMC6233681, DOI: 10.1093/cid/ciy362.
- Distribution of Human Immunodeficiency Virus (HIV) Ribonucleic Acid in Cerebrospinal Fluid and Blood Is Linked to CD4/CD8 Ratio During Acute HIV.Chan P, Patel P, Hellmuth J, Colby DJ, Kroon E, Sacdalan C, Pinyakorn S, Jagodzinski L, Krebs S, Ananworanich J, Valcour V, Spudich S. Distribution of Human Immunodeficiency Virus (HIV) Ribonucleic Acid in Cerebrospinal Fluid and Blood Is Linked to CD4/CD8 Ratio During Acute HIV. The Journal Of Infectious Diseases 2018, 218: 937-945. PMID: 29741638, PMCID: PMC6093332, DOI: 10.1093/infdis/jiy260.
- Single-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV.Farhadian SF, Mehta SS, Zografou C, Robertson K, Price RW, Pappalardo J, Chiarella J, Hafler DA, Spudich SS. Single-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV. JCI Insight 2018, 3 PMID: 30232286, PMCID: PMC6237230, DOI: 10.1172/jci.insight.121718.
- High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection.Kessing CF, Spudich S, Valcour V, Cartwright P, Chalermchai T, Fletcher JL, Nichols C, Josey BJ, Slike B, Krebs SJ, Sailsuta N, Lerdlum S, Jagodzinski L, Tipsuk S, Suttichom D, Rattanamanee S, Zetterberg H, Hellmuth J, Phanuphak N, Robb ML, Michael NL, Ananworanich J, Trautmann L. High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection. Journal Of Acquired Immune Deficiency Syndromes (1999) 2017, 75: 108-117. PMID: 28177966, PMCID: PMC5388590, DOI: 10.1097/QAI.0000000000001301.
- Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy.Rahimy E, Li FY, Hagberg L, Fuchs D, Robertson K, Meyerhoff DJ, Zetterberg H, Price RW, Gisslén M, Spudich S. Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy. The Journal Of Infectious Diseases 2017, 215: 1132-1140. PMID: 28368497, PMCID: PMC5426376, DOI: 10.1093/infdis/jix013.
- Neurologic signs and symptoms frequently manifest in acute HIV infection.Hellmuth J, Fletcher JL, Valcour V, Kroon E, Ananworanich J, Intasan J, Lerdlum S, Narvid J, Pothisri M, Allen I, Krebs SJ, Slike B, Prueksakaew P, Jagodzinski LL, Puttamaswin S, Phanuphak N, Spudich S. Neurologic signs and symptoms frequently manifest in acute HIV infection. Neurology 2016, 87: 148-54. PMID: 27287217, PMCID: PMC4940060, DOI: 10.1212/WNL.0000000000002837.
- Compartmentalized replication of R5 T cell-tropic HIV-1 in the central nervous system early in the course of infection.Sturdevant CB, Joseph SB, Schnell G, Price RW, Swanstrom R, Spudich S. Compartmentalized replication of R5 T cell-tropic HIV-1 in the central nervous system early in the course of infection. PLoS Pathogens 2015, 11: e1004720. PMID: 25811757, PMCID: PMC4374811, DOI: 10.1371/journal.ppat.1004720.
Clinical Trials
| Conditions | Study Title |
|---|---|
| Diseases of the Nervous System; HIV/AIDS; Infectious Diseases; COVID-19 Inpatient; COVID-19 Outpatient | HIV Associated Reservoirs and Comorbidities (The HARC Plus Study) |
| Diseases of the Respiratory Systems; COVID-19 Inpatient; COVID-19 Outpatient | A Study Tracking Health Care Workers Exposed to COVID-19 |
| HIV/AIDS | Mechanisms of HIV latency |
| HIV/AIDS; Immune System; Infectious Diseases | Establish and Characterize an Acute HIV Infection Cohort in a High Risk Population |