About

Joseph Witztum is a faculty member at UCSD in the School of Medicine, specifically within the Vc-health Sciences. His research activities focus on the pivotal role of oxidation-specific epitopes in cardiovascular disease (CVD) and non-alcoholic steatohepatitis (NASH). His work involves investigating immune mechanisms in atherosclerosis and inflammation, with a particular emphasis on the development of therapeutic strategies such as vaccines to inhibit atherosclerosis. Witztum's research also explores the effects of oxidized phospholipids, lipoprotein(a), and other lipid-related factors on cardiovascular outcomes, as well as the role of immune responses in neurodegeneration and metabolic diseases. His extensive funding history includes multiple NIH grants where he serves as principal investigator, highlighting his leadership in advancing understanding of lipid oxidation, immune responses, and their implications for cardiovascular and metabolic diseases.

Research topics

• Cancer research
• Medicine
• Biochemistry
• Immunology
• Internal medicine
• Biology
• Chemistry
• Cell biology
• Endocrinology
• Genetics
• Cardiology
• Pathology

Selected publications

• Tissue tension fosters macrophage-driven lipid peroxidation-induced DNA damage

  Cancer Cell · 2026-04-01

  articleOpen access
  PublisherOA PDFDOI

• Prevalence, baseline characteristics, and reclassification of indeterminate genetic results in patients eligible for the Balance trial with olezarsen

  Journal of clinical lipidology · 2025-05-01 · 1 citations

  article
  PublisherDOI

• Therapeutic Plasma Exchange and Evinacumab for Homozygous Familial Hypercholesterolemia

  JACC Case Reports · 2025-12-10

  articleOpen access

  BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is challenging to treat, requiring intensive lipid-lowering therapy often with novel therapies like evinacumab (angiopoietin-like 3 (ANGPLT3) inhibitor) and procedures like lipoprotein apheresis or therapeutic plasma exchange. CASE SUMMARY: A 47-year-old woman with HoFH and recurrent atherosclerotic cardiovascular disease events presented with intolerance to multiple lipid-lowering therapies and lipoprotein apheresis. She was treated with therapeutic plasma exchange and maximally-tolerated pharmacotherapies, including evinacumab. Treatment was successful but required medical flights every 2 weeks and premedication to prevent anaphylactoid-like reactions. DISCUSSION: Novel therapies like evinacumab and less-frequently used treatments like therapeutic plasma exchange are important options for patients with HoFH experiencing intolerance to standard lipid-lowering therapies. Premedications can be used to manage allergic and allergy-like reactions. TAKE-HOME MESSAGES: Persistence and use of combination therapies are required in treating HoFH, especially when patients experience intolerance to commonly used treatments. Premedications can prevent allergic and allergy-like reactions to therapies in HoFH.

  PublisherDOI

• EFFECT OF OLEZARSEN ON LIPOPROTEIN-ASSOCIATED APOC-III IN PATIENTS WITH FAMILIAL CHYLOMICRONEMIA SYNDROME

  Journal of the American College of Cardiology · 2025-03-29

  articleOpen access
  PublisherDOI

• DIFFERENTIAL RESPONSES IN APOC-III AND TRIGLYCERIDE LOWERING IN FAMILIAL CHYLOMICRONEMIA SYNDROME DIAGNOSED BY GENETIC VERSUS NON-GENETIC CRITERIA

  Journal of the American College of Cardiology · 2025-03-29

  articleOpen accessSenior author
  PublisherDOI

• Epigenetic silencing of interleukin-10 by host-derived oxidized phospholipids supports a lethal inflammatory response to infections

  Immunity · 2025-07-17 · 5 citations

  articleOpen access
  PublisherOA PDFDOI

• Familial chylomicronemia syndrome and treatments to target hepatic APOC3 mRNA

  Atherosclerosis · 2025-01-29 · 12 citations

  reviewSenior author
  PublisherDOI

• Oxidized phosphatidylcholines deposition drives chronic neurodegeneration in a mouse model of progressive multiple sclerosis via IL-1β signaling

  Nature Neuroscience · 2025-12-01

  article
  PublisherDOI

• Oxidized Phospholipids, Lipoprotein(a), and Cardiovascular Outcomes After Acute Coronary Syndrome

  Circulation · 2025-12-01 · 3 citations

  article

  BACKGROUND: Oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) reflect pro-inflammatory properties of Lp(a) (lipoprotein(a)). The effect of OxPL-apoB on major adverse cardiovascular events (MACE) in patients with acute coronary syndrome in recent the era is not known. METHODS: OxPL-apoB levels and Lp(a) were measured in 11 630 participants before and 5185 participants 4 months after randomization to alirocumab or placebo in the ODYSSEY OUTCOMES trial. Proportional hazards models adjusted for baseline covariates evaluated associations between log 2 -transformed OxPL-apoB and Lp(a) with MACEs. Interactions between the 2 biomarkers and treatment were also evaluated. RESULTS: Participants were followed for a median 2.9 years; the median age was 58 years, and 23.9% were female. Alirocumab reduced median placebo-adjusted OxPL-apoB by 13.0% and Lp(a) by 26.2% (both P <0.0001). In the placebo group, a doubling of baseline OxPL-apoB was associated with a hazard ratio (HR) of 1.081 (95% CI, 1.026–1.139; P =0.0034) for MACEs. Addition of Lp(a) to the model relegated the relationship of OxPL-apoB insignificant. In the alirocumab group, neither OxPL-apoB nor Lp(a) remained significantly associated with MACEs. A significant 3-way interaction was present among continuous log 2 OxPL-apoB, Lp(a) stratified at the median, and treatment group on MACEs ( P interaction =0.0023) so that, in the placebo group, increasing OxPL-apoB was associated with higher risk of MACEs when Lp(a) was below the median concentration but not above. In the alirocumab group, OxPL-apoB was not related to MACE risk irrespective of Lp(a) concentration. CONCLUSIONS: In patients with recent acute coronary syndrome receiving optimized statin treatment, elevated OxPL-apoB levels predicted MACEs, a relationship abrogated by alirocumab. The interaction of OxPL-apoB and Lp(a) in the placebo group indicates that OxPL-apoB independently predicts MACEs when Lp(a) levels are relatively low. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT001747 and NCT01663402.

  PublisherDOI

• Anti-OXPL Antibodies Modulates Pathways Driving COPD Pathophysiology

  American Journal of Respiratory and Critical Care Medicine · 2025-05-01

  article

  Abstract Introduction During oxidative stress and chronic inflammation, endogenous oxidized phospholipids (OXPL) are produced driving inflammatory responses in immune as well as non-immune cells. Patients with COPD are associated with an increase in OXPL driving poor pulmonary anti-bacterial innate defences, inflammation and epithelium damage. E06, a natural murine monoclonal IgM antibody, selectively interacts with the phosphocholine head group of oxidized phospholipids and is reported to inhibit the pro-inflammatory effects of OxPLs. We have developed humanized IgG1 and mouse IgG2b anti-OXPL antibodies with similar specificity but higher affinity than the murine E06. Methods • Lung tissues obtained from Human COPD patients and control, or mouse cigarette smoke models were immunohistochemically stained with anti-OXPL antibodies to evaluate OXPL expression. • Human monocytes/macrophages were treated with OXPL in the presence or absence of LPS and the effect of anti-OXPL antibodies on cytokines levels were evaluated. • Effect of anti-OXPL antibodies was evaluated on phagocytosis of bacteria in monocyte/macrophage in the presence or absence of OXPL. • Modulation of epithelium regeneration (scratch assay) by OXPL in an epithelial cell line was evaluated in the presence or absence of anti-OXPL biologics. Results We report that stimulation of human monocytes with OXPL (OXPAPC): • Enhances LPS-induced proinflammatory cytokine while inhibits IL10 • Inhibits bacterial phagocytosis • Blocks wound healing in epithelium scratch assay. We will present data showing the profile of our anti-OXPL antibodies and E06 in in vitro and in vivo models systems supporting the potential for anti-OXPL antibodies in modulating pathological pathways associated with COPD. Furthermore, we will share data showing localisation of OXPL in the lung tissue from a murine Cigarette Smoke model of lung inflammation and COPD patients. Conclusion: Our data strongly support the development of our human anti-OXPL IgG1 for COPD to improve bacterial clearance, anti-inflammatory pathways, and epithelium damage associated with COPD pathology.

  PublisherDOI

Recent grants

• NIH Grant R01HL069464

  NIH · $1.5M · 2005

• NIH Grant R01HL086559

  NIH · $2.0M · 2013

• NIH Grant M01RR000827

  NIH · $28.9M · 2010

• NIH Grant P50HL014197

  NIH · $22.0M · 1997

• NIH Grant U54GM069338

  NIH · $139.8M · 2014

Frequent coauthors

• Sotirios Tsimikas

  University of California, San Diego

  950 shared

• Elizabeth R. Miller

  239 shared

• Stefan Kiechl

  Innsbruck Medical University

  226 shared

• Johann Willeit

  Innsbruck Medical University

  225 shared

• Peter Libby

  Universidade de São Paulo

  194 shared

• Ayelet Gonen

  University of California, San Diego

  182 shared

• Peter Santer

  Krankenhaus Bruneck

  166 shared

• Raimund Pechlaner

  Innsbruck Medical University

  166 shared

Education

• M.D.

  University of California, San Diego

• B.A.

  University of California, San Diego