Hepatitis B and C—A Closer Look at NIAID Research to Accelerate Elimination

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Viral hepatitis is an inflammatory liver disease caused by infection with any of the known hepatitis viruses—A, B, C, D, and E. Most of the global viral hepatitis burden is from hepatitis B and C, which affect 354 million people and result in 1.1 million deaths annually. The Centers for Disease Control and Prevention estimates that in 2020 there were 14,000 and 50,300 new acute infections of hepatitis B and C in the United States, respectively, while at least 880,000 people in the country were living with chronic (long-term) hepatitis B and 2.4 million people had chronic hepatitis C. About half of those with viral hepatitis are unaware of their infection. Chronic and persistent inflammation from the disease can lead to liver failure, cirrhosis, or liver cancer. Viral hepatitis affects all ages and there are pronounced inequities in disease outcomes in the United States. Hepatitis B and C disproportionately affect people living with HIV, and HIV increases the rate of complications and death in people with viral hepatitis.

On this World Hepatitis Day, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, shares a snapshot of its investments in basic (laboratory), preclinical (laboratory/animal), and clinical (human) research to improve screening, prevention and treatment for hepatitis B and C. Scientists in the Hepatic Pathogenesis and Structural Virology sections of NIAID’s Laboratory of Infectious Diseases conduct basic and translational research to better understand hepatitis B and C disease progression, clarify the role of hepatitis viruses in liver cancer, and inform discovery of new vaccines, medicine and technologies. Both NIAID’s Division of AIDS (DAIDS) and the Division of Microbiology and Infectious Disease (DMID) support scientific programs focused on hepatitis B and C research and curative strategies, reflecting the widespread impact of viral hepatitis and the urgent need for safe and effective interventions.

Finding a hepatitis B cure

Hepatitis B continues to cause disease and death even though a highly effective preventive vaccine has been available for decades. Some people with acute hepatitis B can naturally clear the infection. In others, chronic HBV requires lifelong treatment to suppress the virus. More research is need to identify novel therapeutic options and strategies to minimize the treatment burden and, ideally, identify a cure for hepatitis B. NIAID is supporting research on a variety of basic, translational and therapeutic science concepts designed to cure hepatitis B, including in people with HIV. DMID recently announced an initiative to develop new antiviral drugs that can eliminate hepatitis B genetic material from infected cells, and DAIDS is complementing that work with clinical studies of therapeutic agents and vaccines that will include evaluation of their safety and efficacy in people living with HIV.

Streamlining the hepatitis C response

In 2011, direct-acting antivirals (DAA) revolutionized hepatitis C therapy and have since been observed to cure 95% of cases. Despite DAA availability for more than a decade, only one in three people in the United States diagnosed with hepatitis C receive curative treatment. These circumstances underscore the importance of increasing access to and convenience of diagnosis and treatment, as well as the need for a preventive vaccine. Developing a hepatitis C vaccine is challenging because of the genetic diversity of hepatitis C circulating in the population, necessitating broadly reactive vaccine technology. DMID awarded multiple grants to advance new hepatitis C vaccine designs in 2021. To better enable people to know their hepatitis C status, NIAID and other NIH institutes are supporting discovery of improved point-of-care hepatitis C testing that could be used in community and healthcare settings alike, and eliminate the need to wait for laboratory-based diagnostics. They are also supporting development of self-testing technology that people can use to screen themselves. DAIDS will soon launch an initiative to develop long-acting DAAs that could reduce the number of doses required for a full course of therapy. A recent NIAID-supported study showed even with an existing 84-tablet DAA regimen, most people with hepatitis C experienced favorable treatment outcomes without in-person healthcare visits for the duration of treatment. These innovations in diagnostics and treatment strategies aim to enable a “single-encounter cure” wherein a person could learn their hepatitis C status and collect their treatment in one healthcare visit.

These research priorities are among the current efforts in NIAID’s 60-year pursuit of scientific advances to improve the health outcomes of people with viral hepatitis. For more information on US government research to help eliminate viral hepatitis, please visit:

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IAS 2023—HIV Vaccines, bNAbs, and an Update from NIH’s Office of AIDS Research

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This blog is cross-posted from HIV.gov. 

On Tuesday at the International AIDS Society’s 12th Conference on HIV Science (IAS 2023), HIV.gov continued our conversations about research highlights, including a focus on the latest about HIV vaccines. We also heard an update from the NIH Office of AIDS Research.

NIH’s Carl Dieffenbach, Ph.D., Director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases (NIAID), spoke with Louis Shackelford, M.P.H., about HIV vaccine studies being discussed at IAS 2023 and potential roles for broadly neutralizing antibodies (or bNAbs). Louis is the Acting Director for External Relations at the NIH-supported HIV Vaccine Trials Network (HVTN) and COVID-19 Prevention Network. Noting it is an exciting time in HIV vaccine research, Carl explained that scientists are exploring how to take what we have learned about bNAbs, which prevented acquisition of some HIV strains, and turn that into an HIV vaccine. In addition, Carl and Louis discussed how bNAbs are being studied for use in HIV treatment and even, possibly, a cure. View their conversation below:

Bill Kapogiannis, M.D., Acting Director of NIH’s Office of AIDS Research (OAR), spoke with Catey Laube, Section Chief for HIV, STIs, Allergy, Immunology, and Transplantation in NIAID’s Office of Communications and Government Relations. OAR coordinates the scientific, budgetary, legislative, and policy components of HIV/AIDS research across NIH’s institutes and centers. Bill discussed the importance of the results from the NIH-supported REPRIEVE trial presented yesterday at the conference. The global study found that statins, a class of cholesterol-lowering medications, may offset the elevated risk of cardiovascular disease experienced by people with HIV by more than a third, potentially preventing one in five major cardiovascular events (e.g., heart attack or stroke) or premature deaths in this population. He noted that these important findings have implications for clinical guidelines for the care of people with HIV. Bill also observed that the findings are relevant to two of OAR’s signature programs: HIV and Aging, since the study population was people with HIV ages 40-75, and HIV and Women, since the results were equally applicable to women. View their conversation below:

IAS 2023, convening in Brisbane, Australia, features the latest advances in basic, clinical, and operational HIV research and seeks to move science into policy and practice. The conference features seven plenary sessions, more than 60 symposia and oral abstract sessions, hundreds of poster sessions, and many satellite sessions featuring highly diverse and cutting-edge research. Many of the studies that are being presented have been conducted by or funded by federal partners, including NIH, CDC, PEPFAR, DoD, and others.

As is the custom in Australia, HIV.gov acknowledges the Jagera and Turrbal people as the Traditional Custodians of Meanjin (Brisbane), the land on which IAS 2023 is taking place. We pay our respects to Jagera and Turrbal elders past, present, and emerging.

Follow all of our conversations from IAS 2023 this week here on the blog as well as on on HIV.gov’s Facebook, Instagram, and Twitter, and on the LinkedIn account of the HHS Office of Infectious Disease and HIV/AIDS Policy.

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IAS Conference Highlights—Heart Disease Prevention for People with HIV, Long-acting HIV Prevention and Treatment

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This blog is cross-posted from HIV.gov.

During the first full day of sessions at the International AIDS Society’s 12th Conference on HIV Science (IAS 2023), HIV.gov shared conversations on important study findings about reducing cardiovascular disease among people with HIV and the latest developments with long-acting prevention and treatment options that could one day become safe and effective alternatives to daily oral pills.

NIH’s Carl Dieffenbach discussed findings presented today about the NIH-supported Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) trial, a global study that demonstrated a daily statin medication reduces the increased risk of cardiovascular disease experienced by people living with HIV. (Learn more in this NIH news release published today.) Dr. Dieffenbach is the Director of the Division of AIDS at NIH’s National Institute of Allergy and Infectious Diseases (NIAID). He spoke today with Molly Moon, M.S.W., Deputy Director of the NIH-supported Office of HIV/AIDS Network Coordination. They also discussed progress reported at IAS 2023 from several studies investigating long-acting HIV prevention and treatment options, including some that were presented in a plenary session that Carl chaired today. Carl summarized that long-acting options are moving toward better drugs with lower doses and longer durations. View their conversation below:

To learn more about what the results of the REPRIEVE trial mean, Molly also spoke with Steven Grinspoon, M.D., professor of medicine at Harvard University and chief of the metabolism unit at Massachusetts General Hospital, who led the REPRIEVE study. Steven highlighted that this global trial, involving participants in 12 countries, found that the use of the statin pitavastatin calcium reduced the risk of major adverse cardiovascular events—including heart attack, stroke, and cardiovascular death—among people with HIV by 35%. He added that the study found that the intervention was equally efficacious among men and women. Simultaneous to their presentation at IAS 2023, the REPRIEVE study findings were published in the New England Journal of Medicine.

IAS 2023, convening in Brisbane, Australia, features the latest advances in basic, clinical, and operational HIV research and seeks to move science into policy and practice. The conference features seven plenary sessions, more than 60 symposia and oral abstract sessions, hundreds of poster sessions, and many satellite sessions featuring highly diverse and cutting-edge research. Many of the studies that will be presented have been conducted by or funded by federal partners, including NIH, CDC, PEPFAR, DoD, and others.

As is the custom in Australia, HIV.gov acknowledges the Jagera and the Turrbal people as the Traditional Custodians of Meanjin (Brisbane), the land on which IAS 2023 is taking place. We pay our respects to Jagera and Turrbal elders past, present, and emerging.

Follow all of our conversations from IAS 2023 this week on HIV.gov’s Facebook, Instagram, and Twitter, and on the LinkedIn account of the HHS Office of Infectious Disease and HIV/AIDS Policy.

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National and Regional Biocontainment Research Facilities

The National Biocontainment Laboratories (NBLs) and Regional Biocontainment Laboratories (RBLs) provide BSL4/3/2 and BSL3/2 biocontainment facilities, respectively, for research on biodefense and emerging infectious disease agents.  

Research Synthetic Nucleic Acid Platforms to Fight HIV

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Apply for a grant to advance synthetic nucleic acid platforms for HIV prevention, treatment, and cure through the new NIAID notice of funding opportunity (NOFO): Synthetic Nucleic Acid Platforms for HIV-1 (SNAPH) (R61/R33, Clinical Trial Not Allowed).

Scientific Synopsis

In your application, describe how you will advance synthetic nucleic acid platforms (SNAP) for the rapid development and iterative testing of active and passive immunization strategies for HIV prevention, treatment, and cure. This includes testing of prophylactic and therapeutic vaccines and the delivery of broadly neutralizing antibodies (bNAb) and bNAb derivatives.

Propose research to apply newly developed immunological tools and expand understanding of the immune response to vaccination at the molecular level. How will you overcome existing challenges to the quality and durability of T-cell and antibody responses to HIV as well as the ability of SNAP to deliver physiologically relevant titers of bNAbs for sustained periods? Describe how you will evaluate the extent to which DNA/RNA technologies can:

  • Be applied to various types of HIV vaccine immunogens and complex regimens.
  • Elicit stronger, broader, and longer-lasting HIV-specific immune responses.
  • Be used in combination with other platforms.
  • Support the delivery of bNAbs or bNAb derivatives for the prevention, treatment, or cure of HIV.

To strengthen the likelihood of successful clinical translation, you must include a translational partner or partners as a significant collaborator in your application. Find further details in the Research Objectives header in Section I of the NOFO, including definitions for translational partner and collaboration, examples of research projects that would be in scope, and nonresponsive scientific areas.

Note that while clinical trials are not allowed for this NOFO, NIAID encourages you to use samples from clinical trials supported by other funding mechanisms. Animal research is allowed, including the use of small animal models and nonhuman primates with HIV, SIV, or SHIV challenges.

Award and Application Specifics

Due to the high-risk, high-impact nature of the research, the SNAPH NOFO uses the R61/R33 phased innovation grant award mechanism:

  • R61 phase. NIAID will provide support for up to 3 years for hypothesis-driven design, optimization, and characterization of SNAP for the delivery of synthetic nucleic acid immunogens, bNAbs, and/or bNAb derivatives.
  • Optional R33 phase. NIAID may choose to provide up to 2 years of subsequent support for additional activities as appropriate. For example, NIAID may support work to test your SNAP delivery approach in relevant animal models and evaluate product potential. NIAID will review and negotiate R33 phase milestones before award.

This opportunity has a single due date; be sure to apply by August 2, 2023, at 5 p.m. local time of the applicant organization. Submit your optional Letter of Intent 30 days before you apply.

Well before you apply, we encourage you to reach out to the following NIAID scientific/research program contacts to discuss your project plans:

  • For immunology and design of prophylactic immunomodulators, antibodies, and immunogens: Dr. Angela Malaspina., angela.malaspina@nih.gov or 240-292-6130.
  • For immunology and design of therapeutic immunomodulators, antibodies, and immunogens: Dr. Steve Smiley, stephen.smiley@nih.gov or 240-627-3071.
  • For therapeutic interventions in animal studies: Dr. Brigitte Sanders, brigitte.sanders@nih.gov or 240-627-3209.

Direct your peer review or grants management questions to the relevant contacts in Section VII of the NOFO.

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AIDS Imaging Research—Integrated Research Facility at Fort Detrick

The AIDS Imaging Research Section (AIRS) leverages preclinical and translational molecular imaging to study the pathogenesis of human immunodeficiency virus (HIV) infection using the simian/simian-human immunodeficiency virus (SIV/SHIV) nonhuman primate model.

Sinu P. John, Ph.D.

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Signaling Systems Section
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Our research focuses primarily on identification of cell intrinsic factors (protein coding and non-coding genes) associated with regulation of macrophage signaling. We use high throughput genome-wide techniques such as RNAi screening, CRISPR screening, RNA-seq, ATAC-seq, etc. to identify and characterize the genes and gene-regulatory mechanisms that modulate the immune response in macrophage cells. In addition, we study the role of various external factors (environmental pollutants, drugs, diet, etc.) that modulate the immune response in macrophages with an emphasis to develop therapeutic candidates for the treatment of infectious and immune diseases. We use both bacterial and several emerging viral models such as HIV, Influenza, SARS-CoV-2, etc. to study the impact of immune regulation by various intrinsic and external factors.

Selected Publications

John SP, Singh A, Sun J, Pierre MJ, Alsalih L, Lipsey C, Traore Z, Balcom-Luker S, Bradfield CJ, Song J, Markowitz TE, Smelkinson M, Ferrer M, Fraser IDC. Small-molecule screening identifies Syk kinase inhibition and rutaecarpine as modulators of macrophage training and SARS-CoV-2 infection. Cell Rep. 2022 Oct 4;41(1):111441.

John SP, Sun J, Carlson RJ, Cao B, Bradfield CJ, Song J, Smelkinson M, Fraser IDC. IFIT1 Exerts Opposing Regulatory Effects on the Inflammatory and Interferon Gene Programs in LPS-Activated Human Macrophages. Cell Rep. 2018 Oct 2;25(1):95-106.e6.

John SP, Chin CR, Perreira JM, Feeley EM, Aker AM, Savidis G, Smith SE, Elia AE, Everitt AR, Vora M, Pertel T, Elledge SJ, Kellam P, Brass AL. The CD225 domain of IFITM3 is required for both IFITM protein association and inhibition of influenza A virus and dengue virus replication. J Virol. 2013 Jul;87(14):7837-52.

Zhu J, Gaiha GD, John SP, Pertel T, Chin CR, Gao G, Qu H, Walker BD, Elledge SJ, Brass AL. Reactivation of latent HIV-1 by inhibition of BRD4. Cell Rep. 2012 Oct 25;2(4):807-16.

Everitt AR, Clare S, Pertel T, John SP, Wash RS, Smith SE, Chin CR, Feeley EM, Sims JS, Adams DJ, Wise HM, Kane L, Goulding D, Digard P, Anttila V, Baillie JK, Walsh TS, Hume DA, Palotie A, Xue Y, Colonna V, Tyler-Smith C, Dunning J, Gordon SB; GenISIS Investigators; MOSAIC Investigators; Smyth RL, Openshaw PJ, Dougan G, Brass AL, Kellam P. IFITM3 restricts the morbidity and mortality associated with influenza. Nature. 2012 Mar 25;484(7395):519-23.

Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E, Adams DJ, Xavier RJ, Farzan M, Elledge SJ. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell. 2009 Dec 24;139(7):1243-54.

Visit PubMed for a complete publication listing.

Major Areas of Research
  • Genes and epigenetic states modulating macrophage signaling and function
  • Identification and characterization of trained immunity stimuli
  • Applications of trained immunity in infectious and immune disease

Four Research Areas Comprise NIAID’s 2023 Omnibus Contract Solicitation

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If you can carry out research that supports program objectives of NIAID’s Division of Microbiology and Infectious Diseases (DMID), consider submitting a proposal through the 2023 NIAID Omnibus Broad Agency Announcement (BAA) contract solicitation.

DMID will use this BAA to advance the research and development of promising candidate vaccines, therapeutics, and diagnostics for biodefense, emerging infectious diseases, and pandemic preparedness.

As we summarize below, the 2023 BAA covers four distinct research areas. You may respond to one, any combination of, or all the research areas. For each research area, be sure to present separate, detailed technical and business proposals designed to meet the objectives described.

For all four research areas:

Research Area 001: Development of Vaccine Candidates for Biodefense and Emerging Infectious Diseases

  • Description: Supports advancing vaccine candidates, technologies, and platforms that could be deployed against agents that include category A, B, and C NIAID Emerging Infectious Diseases and Pathogens.
  • Number of Awards, Total Costs: For fiscal year (FY) 2024, NIAID estimates it will award up to $12.8 million total for the non-severable base period of five or six cost-reimbursement type contracts across research areas 001, 002, and 004.
  • Due Date: April 11, 2023, by 3 p.m. Eastern Time.

Research Area 002: Development of Therapeutic Candidates for Biodefense, Antimicrobial Resistant (AMR) Infections, and Emerging Infectious Diseases

  • Description: Supports the development of promising new therapeutics to address infections and diseases caused by NIAID Emerging Infectious Diseases and Pathogens (including category A, B, and C priority pathogens) and selected bacterial and fungal pathogens identified in the CDC 2019 Antibiotic Resistance Threats in the United States report.
  • Number of Awards, Total Costs: For FY 2024, NIAID estimates it will award up to $12.8 million total for the non-severable base period of five or six cost-reimbursement type contracts across research areas 001, 002, and 004.
  • Due Date: April 11, 2023, by 3 p.m. Eastern Time.

Research Area 003: The Antiviral Program for Pandemics (APP): Development of Antivirals for RNA Viral Families of Pandemic Potential

  • Description: Supports the development of antivirals as described in the Antiviral Program for Pandemics. NIAID encourages proposals to develop safe and effective antivirals to combat SARS-CoV-2, the virus that causes COVID-19, as well as to build sustainable platforms for targeted drug discovery and development of a robust pipeline of antivirals against viruses with pandemic potential.
  • Number of Awards, Total Costs: For FY 2024, NIAID estimates it will award up to $3.5 million total for the non-severable base period of one cost-reimbursement type contract.
  • Due Date: March 13, 2023, by 3 p.m. Eastern Time.

Research Area 004: Development of In Vitro Diagnostics for Biodefense, AMR Infections, and Emerging Infectious Diseases

  • Description: Supports the development of promising diagnostics technologies for detection of signatures from biothreat pathogens and pathogens causing emerging, reemerging, and AMR infectious diseases, and for pandemic preparedness.
  • Number of Awards, Total Costs: For FY 2024, NIAID estimates it will award up to $12.8 million total for the non-severable base period of five or six cost-reimbursement type contracts across research areas 001, 002, and 004.
  • Due Date: April 11, 2023, by 3 p.m. Eastern Time.

Find complete details in the solicitation itself as well as any amendments issued since this article was published.

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New Solicitation Focuses on Development of Cellular Immunology Core

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NIAID supports basic research on microbiology and immunology that may lead to the development of vaccines, therapeutics, and medical diagnostics for the prevention, treatment, and diagnosis of infectious and immune-mediated diseases.

NIAID’s Division of AIDS is seeking a partner to operate the Cellular Immunology Core Laboratory, which will conduct, analyze, develop, optimize, and validate cellular immunologic assays for HIV, Simian Immunodeficiency Virus, Mycobacterium tuberculosis, and other pathogens, to be performed on fresh and frozen preclinical samples.

A new request for proposals (RFP) seeks contractors who can do the following:

  • Conduct validated immunological assays using good laboratory practice (GLP)-like processes
  • Perform data analyses
  • Receive, store, catalog, track, and maintain an inventory of the specimens for evaluation
  • Manage, report, and deposit study data
  • Perform project management activities related to contract activities
  • Conduct initial and final transition activities, as needed

The contractor shall use current state-of-the-art technologies, including, at a minimum, ELISPOT, intracellular cytokine staining, flow cytometry, cell sorting, tetramer staining, and other assays to accomplish the technical objectives, and shall incorporate new and optimized technologies for assay development into contract activities when appropriate. Assays shall incorporate appropriate positive and negative controls using reference panels to define background and dynamic range and shall demonstrate reproducibility and consistency.

Additionally, the contractor shall also use state-of-the-art methods to analyze the data generated by the conduct of the assays, which may require different data analysis methods/platforms as appropriate for each type of assay. Data analyses may require generating publication quality figures, when directed by the contracting officer’s representative. Lastly, an independent Quality Assurance Program, not associated with the contract, shall conduct regular inspections to review facilities, equipment, personnel, methods, practices, and records.

Details and Due Date

Read the RFP Cellular Immunology Core Laboratory for complete details.

NIAID anticipates awarding one cost reimbursement, level-of-effort (term) type contract for a 1-year base period plus six 1-year options for a total possible performance period of 7 years, beginning on March 1, 2024.

Proposals are due on March 17, 2023, by 3 p.m. Eastern Time. Submit applications online through NIH’s electronic Contract Proposal Submission (eCPS) site.

Send inquiries to Kimberly Dormer, NIAID’s contract specialist for this opportunity, at kimberly.dormer@nih.gov.

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Fernanda D. Young, M.D.

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Food Allergy Research Section
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Food allergy is a significant health problem in the United States, affecting children and adults, both immune competent and immune compromised. The overall goal of the Food Allergy Research Section (FARS) is to understand the genetic, immunologic, and biochemical pathways that lead to the development of food allergy and how they can be modified for therapeutic benefit. We aim to achieve this goal using a multifaceted approach with studies involving both patients and animal models of their diseases.

Our team in particular is studying why only some patients who have detectable IgE to specific foods experience an allergic reaction when they eat the food, and we are working to identify immunologic markers that can predict the severity and persistence of food allergy.

By achieving a greater understanding of the key environmental, immunologic, and biochemical pathways that drive the development of food allergy, we will be able to develop novel interventions that are based on a advanced understanding of disease pathogenesis.

Selected Publications

Tsao LR, Young FD, Otani IM, Castells MC. Hypersensitivity Reactions to Platinum Agents and Taxanes. Clin Rev Allergy Immunol. 2022 Jun;62(3):432-448.

Hubbard TP, Billings G, Dörr T, Sit B, Warr AR, Kuehl CJ, Kim M, Delgado F, Mekalanos JJ, Lewnard JA, Waldor MK. A live vaccine rapidly protects against cholera in an infant rabbit model. Sci Transl Med. 2018 Jun 13;10(445):eaap8423.

Dörr T, Delgado F, Umans BD, Gerding MA, Davis BM, Waldor MK. A Transposon Screen Identifies Genetic Determinants of Vibrio cholerae Resistance to High-Molecular-Weight Antibiotics. Antimicrob Agents Chemother. 2016 Jul 22;60(8):4757-63.

Dörr T, Alvarez L, Delgado F, Davis BM, Cava F, Waldor MK. A cell wall damage response mediated by a sensor kinase/response regulator pair enables beta-lactam tolerance. Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):404-9.

Malen R, Knerr S, Delgado F, Fullerton SM, Thompson B. Rural Mexican-Americans' perceptions of family health history, genetics, and disease risk: implications for disparities-focused research dissemination. J Community Genet. 2016 Jan;7(1):91-6.

Delgado F, Tabor HK, Chow PM, Conta JH, Feldman KW, Tsuchiya KD, Beck AE. Single-nucleotide polymorphism arrays and unexpected consanguinity: considerations for clinicians when returning results to families. Genet Med. 2015 May;17(5):400-4.

Visit PubMed for a complete publication listing.

Additional Information
Major Areas of Research

Dr. Young’s work places an emphasis on clinical research to identify contributory factors to:

  • food allergy and allergic disease
  • transplant associated food allergy
  • drug allergy and drug reactions