Featured CDSI Research of Dr. Elizabeth Phillips

Dr. Elizabeth Phillips is an international leader in drug hypersensitivity, studying genetic risk, mechanisms, and outcomes of severe and life-threatening immune-mediated adverse drug reactions. She continues to translate this knowledge into prescribing safer drugs for patients and families.

Elizabeth J. Phillips, MD, FRCPC, FRACP, FIDSA, FAAAAI, is the John A. Oates Chair in Clinical Research; Professor of Medicine, Dermatology; Pharmacology; Pathology, Microbiology and Immunology; and Founder and Director, Center for Drug Safety and Immunology at Vanderbilt University Medical Center.

Expertise:

Dr. Phillips is a world leader in translational approaches to drug hypersensitivity and has pioneered the discovery and implementation of immunogenomic predictors, immunopathogenesis, and novel technologies to improve the safety of drugs into clinical practice.

Current Focus:

Dr. Phillips is the Principal Investigator on several NIH-funded research projects to define genetic and other markers that can lead to the prediction, prevention, and earlier diagnosis of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.

Below are the studies in which Dr. Phillips is the principal investigator (PI), followed by studies she co-investigates.

North American Therapeutics in Epidermal Necrolysis Syndrome (NATIENS)

The NATIENS study is a first-of-its-kind phase III multicenter randomized clinical trial to establish the most clinically effective therapy for SJS/TEN. There is a lack of evidence-based treatment for SJS/TEN, which Dr. Phillip seeks to address through this clinical trial. This study assesses three therapeutic modalities: cyclosporine, etanercept, and standard supportive care. A critical outcome is the time to complete re-epithelialization across treatment modalities.

Collected patient samples include DNA, RNA, plasma, serum, blister fluid cells and supernatant, sloughed epidermis, and punch biopsies of skin. The collected samples will be biobanked for future high-resolution SLA sequencing, cytokine profiling, and single-cell multidimensional analyses to determine the biological markers that may predict the risk and severity of SJS/TEN. Findings from this first-of-its-kind study may provide insights into the management and immunopathogenesis of SJS/TEN.

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Understanding and Preventing HLA-associated Drug Reactions

The goal of this study, led by Dr. Phillips, is to determine the mechanistic basis of HLA-associated drug hypersensitivity. HLA alleles help the immune system distinguish between the body’s proteins and proteins made by foreign invaders such as viruses and bacteria. At times, HLA alleles can adversely react to the presence of drugs.

This study includes three critical aims related to the analysis of HLA alleles:

To identify the primary HLA allele and T-cell receptor (TCR) used by pathogenic T cells in drug-hypersensitive patients but not HLA-matched drug-tolerant controls.
To define anti-viral T cells in drug-hypersensitive patients but not HLA risk-allele matched drug-tolerant controls.
To elucidate the anti-viral T cells present in drug-hypersensitive patients that cross-recognize a drug in the context of the HLA risk allele.

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Stevens-Johnson Syndrome (SJS) Survivor Study and DRESS Syndrome Survivor Study

To overcome difficulties in accessing large cohorts of SJS/TEN and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome survivors due to the rarity of these diseases, Dr. Phillips has partnered with the SJS Foundation and the DRESS Syndrome Foundation to develop data and DNA biobanks of SJS/TEN and DRESS syndrome survivors from the foundations’ patient registries.

Consented patients provide medical records confirming their SJS/TEN or DRESS syndrome diagnosis and their DNA through saliva samples. Patients also complete psychometrically validated questionnaires that assess mental and physical health complications. In addition, high-resolution HLA, ERAP, and KIR typing, as well as an expanded multi-ethnic genotyping array (MegaEx), is performed to determine HLA and other genetic risk factors associated with drug-induced SJS/TEN and DRESS syndrome.

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Understanding and Monitoring Drug-induced Anaphylaxis

Anaphylaxis is an acute allergic reaction to an antigen (e.g., medication, food, and bee sting). Even though anaphylaxis can be life-threatening, there is limited knowledge of the risk factors for experiencing this allergic reaction.

The specific aims of this study, spearheaded by Dr. Cosby Stone, Jr. and co-investigated by Dr. Phillips, are to examine patient-specific ecological and immunogenetic risk factors for developing anaphylaxis and to study the natural history of allergic reactions.

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Additional Studies and Registries

Please visit the following study pages to learn more about research in which Dr. Phillips is a co-investigator or local site investigator in an externally-led study:

Immune-mediated Adverse Drug Reactions to Human Immunodeficiency Virus (HIV) and Tuberculosis (TB) Treatments in South Africa (IMARI) run by Dr. Jonny Peter at the University of Cape Town, South Africa.
ABO and Immunogenetic Variation in the Pathogenesis of Heparin-Induced Thrombocytopenia spearheaded by Dr. Jason Karnes at the University of Arizona.
Systemic Allergic Reactions to SARS-CoV-2 Vaccination (SARS-CoV-2) led by Dr. Jane Buckner at the Benaroya Research Institute.
Penicillin Allergy Clinical Decision Rule (PALACE) overseen by Dr. Ana Copaescu, McGill University, Canada, and Dr. Jason Trubiano, Austin Hospital, Doherty Institute, University of Melbourne, Australia.
United States Drug Allergy Registry (USDAR), spearheaded by Dr. Kim Blumenthal and her colleagues at Massachusetts General Hospital.

Registries for severe cutaneous adverse reactions (SCARs):

United States: Massachusetts General Brigham-Severe Cutaneous Adverse Reaction (MGB-SCAR) managed by Dr. Li Zhou.
International Registries and Networks:
- African Severe Cutaneous Adverse Reactions (AFRI-SCAR) Network, of which Dr. Jonny Peter is a founding member
- Australasian Registry for Severe Cutaneous Adverse Reactions (AUS-SCAR) led by Dr. Jason Trubiano.

Publications

See Dr. Phillips' full bibliography here.

Featured CDSI Research of Dr. Elizabeth Phillips

North American Therapeutics in Epidermal Necrolysis Syndrome (NATIENS)

Understanding and Preventing HLA-associated Drug Reactions

Stevens-Johnson Syndrome (SJS) Survivor Study and DRESS Syndrome Survivor Study

Understanding and Monitoring Drug-induced Anaphylaxis

Additional Studies and Registries

Publications

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