About

Alexandra Weiss, MD, is an Assistant Professor of Clinical Medicine in the Department of Medicine at the University of Pennsylvania's Perelman School of Medicine. She specializes in Gastroenterology and is the Epic EHR Physician Lead for the GI division. Dr. Weiss completed her Bachelor of Science in Biomedical Engineering at the University of Virginia in 2006 and earned her MD from Howard University College of Medicine in 2013. Her professional focus includes research on inflammatory bowel disease, ulcerative colitis, Crohn's disease, and related gastrointestinal conditions. She has contributed to numerous publications in her field, emphasizing clinical management and epidemiology of gastrointestinal disorders.

Research topics

• Medicine
• Computer Science
• Internal medicine
• Chemistry
• Demography
• Computational biology
• Molecular biology
• Genetics
• Cell biology
• Biology
• Gastroenterology

Selected publications

• Obscure Small Bowel Bleeding From Visceral Kaposi Sarcoma Without Cutaneous Manifestations

  The American Journal of Gastroenterology · 2025-05-13

  article
  PublisherDOI

• RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice

  Molecular Therapy · 2025-05-09 · 4 citations

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Incidence, Prevalence, and Racial and Ethnic Distribution of Inflammatory Bowel Disease in the United States

  UNC Libraries · 2025-03-21

  articleOpen access
  PublisherDOI

• 2252P Peripheral immunological responses to immunotherapy combined with gemcitabine, nab-paclitaxel, and adaptive stereotactic body radiotherapy in pancreatic cancer (LAPTOP)

  Annals of Oncology · 2025-09-01

  article
  PublisherDOI

• Genetic Ablation of <i>Sarm1</i> Mitigates Disease Acceleration after Traumatic Brain Injury in the <scp>SOD1^G93A</scp> Transgenic Mouse Model of Amyotrophic Lateral Sclerosis

  Annals of Neurology · 2025-01-10 · 3 citations

  articleOpen access

  Objective Approximately 20% of familial cases of amyotrophic lateral sclerosis (ALS) are caused by mutations in the gene encoding superoxide dismutase 1 (SOD1). Epidemiological data have identified traumatic brain injury (TBI) as an exogenous risk factor for ALS; however, the mechanisms by which TBI may worsen SOD1 ALS remain largely undefined. Methods We sought to determine whether repetitive TBI (rTBI) accelerates disease onset and progression in the transgenic SOD1 G93A mouse ALS model, and whether loss of the primary regulator of axonal degeneration sterile alpha and TIR motif containing 1 ( Sarm1 ) mitigates the histological and behavioral pathophysiology. We subjected wild‐type (n = 23), Sarm1 knockout (KO; n = 17), SOD1 G93A (n = 19), and SOD1 G93A xSarm1 KO (n = 26) mice of both sexes to rTBI or sham surgery at age 64 days (62–68 days). Body weight and ALS‐deficit score were serially assessed up to 17 weeks after surgery and histopathology assessed in layer V of the primary motor cortex at the study end point. Results In sham injured SOD1 G93A mice, genetic ablation of Sarm1 did not attenuate axonal loss, improve neurological deficits, or survival. The rTBI accelerated onset of G93A‐SOD1 ALS, as indicated by accentuated body weight loss, earlier onset of hindlimb tremor, and shortened survival. The rTBI also triggered TDP‐43 mislocalization, enhanced axonal and neuronal loss, microgliosis, and astrocytosis. Loss of Sarm1 significantly diminished the impact of rTBI on disease progression and rescued rTBI‐associated neuropathology. Interpretation SARM1‐mediated axonal death pathway promotes pathogenesis after TBI in SOD1 G93A mice suggesting that anti‐SARM1 therapeutics are a viable approach to preserve neurological function in injury‐accelerated G93A‐SOD1 ALS. ANN NEUROL 2025;97:963–975

  PublisherOA PDFDOI

• Identification of selective and non-selective C9ORF72 targeting in vivo active siRNAs

  Molecular Therapy — Nucleic Acids · 2024-08-01 · 9 citations

  articleOpen access

  A hexanucleotide (G4C2) repeat expansion (HRE) within intron one of C9ORF72 is the leading genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). C9ORF72 haploinsufficiency, formation of RNA foci, and production of dipeptide repeat (DPR) proteins have been proposed as mechanisms of disease. Here, we report the first example of disease-modifying siRNAs for C9ORF72 driven ALS/FTD. Using a combination of reporter assay and primary cortical neurons derived from a C9-ALS/FTD mouse model, we screened a panel of more than 150 fully chemically stabilized siRNAs targeting different C9ORF72 transcriptional variants. We demonstrate the lack of correlation between siRNA efficacy in reporter assay versus native environment; repeat-containing C9ORF72 mRNA variants are found to preferentially localize to the nucleus, and thus C9ORF72 mRNA accessibility and intracellular localization have a dominant impact on functional RNAi. Using a C9-ALS/FTD mouse model, we demonstrate that divalent siRNAs targeting C9ORF72 mRNA variants specifically or non-selectively reduce the expression of C9ORF72 mRNA and significantly reduce DPR proteins. Interestingly, siRNA silencing all C9ORF72 mRNA transcripts was more effective in removing intranuclear mRNA aggregates than targeting only HRE-containing C9ORF72 mRNA transcripts. Combined, these data support RNAi-based degradation of C9ORF72 as a potential therapeutic paradigm. A hexanucleotide (G4C2) repeat expansion (HRE) within intron one of C9ORF72 is the leading genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). C9ORF72 haploinsufficiency, formation of RNA foci, and production of dipeptide repeat (DPR) proteins have been proposed as mechanisms of disease. Here, we report the first example of disease-modifying siRNAs for C9ORF72 driven ALS/FTD. Using a combination of reporter assay and primary cortical neurons derived from a C9-ALS/FTD mouse model, we screened a panel of more than 150 fully chemically stabilized siRNAs targeting different C9ORF72 transcriptional variants. We demonstrate the lack of correlation between siRNA efficacy in reporter assay versus native environment; repeat-containing C9ORF72 mRNA variants are found to preferentially localize to the nucleus, and thus C9ORF72 mRNA accessibility and intracellular localization have a dominant impact on functional RNAi. Using a C9-ALS/FTD mouse model, we demonstrate that divalent siRNAs targeting C9ORF72 mRNA variants specifically or non-selectively reduce the expression of C9ORF72 mRNA and significantly reduce DPR proteins. Interestingly, siRNA silencing all C9ORF72 mRNA transcripts was more effective in removing intranuclear mRNA aggregates than targeting only HRE-containing C9ORF72 mRNA transcripts. Combined, these data support RNAi-based degradation of C9ORF72 as a potential therapeutic paradigm.

  PublisherDOI

• Meta-analysis of the Therapeutic Impact of Cannabinoids in Inflammatory Bowel Disease

  Inflammatory Bowel Diseases · 2024-08-28 · 8 citations

  review

  BACKGROUND: With the increasing legalization of medical and recreational cannabis, patients and providers have growing interest in the role of cannabinoids in treating inflammatory bowel disease. Prior meta-analysis has shown inconclusive evidence for efficacy of cannabinoids. We sought to produce an up-to-date meta-analysis that pools new data to evaluate the therapeutic effects of cannabinoids in both Crohn's disease (CD) and ulcerative colitis (UC). METHODS: PubMed, Embase, CENTRAL and CINAHL were queried for randomized-controlled trials evaluating the impact cannabinoids in CD or UC. Random effects modeling was used to compute pooled estimates of risk difference. Heterogeneity was assessed using I2. RESULTS: Eight studies, including 4 studies of CD, 3 studies of UC, and 1 study of both diseases met inclusion criteria. Among 5 studies of CD, a statistically significant decrease in clinical disease activity following intervention was observed (risk ratios [RR], -0.91; 95% CI, CI:1.54 to CI:0.28, I2 = 71.9%). Clinical disease activity in UC was not significantly lower in the pooled analysis (RR, -2.13; 95% CI, -4.80 to 0.55; I2 = 90.3%). Improvement in quality of life (QoL) was observed in both CD and UC combined (RR, 1.79; 95% CI, 0.92-0.2.66; I2 = 82.8%), as well as individually. No differences were observed in the analysis on endoscopic disease activity and inflammatory markers. CONCLUSIONS: This meta-analysis of clinical trials suggests that cannabinoids are associated with improved quality of life in both CD and UC, as well as improved disease activity but not inflammation.

  PublisherDOI

• Quantifying and mitigating motor phenotypes induced by antisense oligonucleotides in the central nervous system

  Molecular Therapy · 2024-10-30 · 24 citations

  articleOpen access

  Antisense oligonucleotides (ASOs) are emerging as a promising class of therapeutics for neurological diseases. When injected directly into cerebrospinal fluid, ASOs distribute broadly across brain regions and exert long-lasting therapeutic effects. However, many phosphorothioate (PS)-modified gapmer ASOs show transient motor phenotypes when injected into the cerebrospinal fluid, ranging from reduced motor activity to ataxia or acute seizure-like phenotypes. Using a behavioral scoring assay customized to reflect the timing and nature of these effects, we show that both sugar and phosphate modifications influence acute motor phenotypes. Among sugar analogs, DNA induces the strongest motor phenotypes while 2'-substituted RNA modifications improve the tolerability of PS ASOs. Reducing the PS content of gapmer ASOs, which contain a stretch of PS-DNA, improves their toxicity profile, but in some cases also reduces efficacy or duration of effect. We show that this acute toxicity is not mediated by major nucleic acid sensing immune pathways. Formulating ASOs with divalent ions before injection and avoiding phosphate-based buffers modestly improved tolerability through mechanisms at least partially distinct from reduced PS content. Overall, our work identifies and quantifies an understudied aspect of oligonucleotide toxicology in the CNS, explores its mechanism, and presents platform-level medicinal chemistry and formulation approaches that improve tolerability of this class of compounds.

  PublisherDOI

• Greater Fatigue and Reduced Neurocognitive Speed With Symptomatic Crohn’s Disease

  Crohn s & Colitis 360 · 2024-12-23

  articleOpen access

  Abstract Background While patients with Crohn’s disease commonly report fatigue, an association of Crohn’s disease with mild neurocognitive impairment has also been suggested. This study investigated the relationship between Crohn’s disease activity, fatigue, and neurocognitive functioning. Methods In this cross-sectional study, adults with Crohn’s disease (n = 25) and healthy controls (n = 26) completed the PROMIS Fatigue 7a form and Multidimensional Fatigue Inventory and neurocognitive testing across 6 domains. Symptomatic and endoscopic remission were assessed with a short Crohn’s Disease Activity Index and Simple Endoscopic Score for Crohn’s Disease. Linear regression adjusting for age and sex was used to compare fatigue and neurocognition among patients with Crohn’s disease versus controls and those with active Crohn’s disease versus those in remission. Results Compared to controls, adults with Crohn’s disease reported greater overall and domain-specific fatigue (general, physical, and mental) (P &amp;lt; .05 for all comparisons). Patients in symptomatic remission had significantly less fatigue (P &amp;lt; .05). No differences were found in neurocognitive accuracy or speed between Crohn’s disease and controls. Disease activity was not associated with accuracy on neurocognitive testing; however, patients with symptomatic Crohn’s disease had longer correct response times for social cognition and episodic memory compared to asymptomatic patients (P &amp;lt; .05). Endoscopic disease activity was associated with longer correct response times for tasks linked to social cognition, episodic memory, and complex cognition (P &amp;lt; .05). These differences persisted after adjusting for fatigue. Conclusions Patients with symptomatic Crohn’s disease experience greater fatigue and have slower response times on neurocognitive testing. However, fatigue does not appear to mediate the slower response times.

  PublisherOA PDFDOI

• Liberation After/life: Narrative Connectivity and Black Women’s Cancer Mortality

  Catalyst Feminism Theory Technoscience · 2024-10-16

  articleOpen access1st authorCorresponding

  This paper explores the hauntology of cancer mortality in the context of the Black feminist struggle for liberation. Looking at the lives and deaths of Audre Lorde and Henrietta Lacks, I argue that transcendent narratives, and the connections they draw between past and future, living and dead, offer a degree off liberatory flight in the face and aftermath of terminal cancer. Narrative connectivity resists the silencing, medicalizing, and structural violence of cancer in the context of a racist medical system, by allowing for Black women, their families, and those who love them to tell their stories, reaching other Black women, rather than being flattened into patients, into single moments in time, into resources for extraction. Instead, through a continuing care network of readers and family, Lacks, Lorde and millions of less famous but no less important Black women who have died from cancer, live on in these moments of interconnectivity through memory, freed from the boundaries of time itself.

  PublisherOA PDFDOI

Frequent coauthors

• Robert H. Brown

  University of Massachusetts Chan Medical School

  18 shared

• Pamela Dominutti

  Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement

  14 shared

• James L. France

  13 shared

• Tom Lachlan‐Cope

  British Antarctic Survey

  11 shared

• Nicholas Wightman

  UMass Memorial Medical Center

  10 shared

• Hélène Tran

  University of Massachusetts Chan Medical School

  9 shared

• James Lee

  9 shared

• Stuart Young

  University of York

  9 shared

Labs

• Weiss LabPI

Education

• B.S., Biomedical Engineering

  University of Virginia

  2006

• M.D.

  Howard University College of Medicine

  2013