Robert T. Schooley

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Robert "Chip" T. Schooley
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Born (1949-11-10) November 10, 1949 (age 73)
NationalityAmerican
Alma materJohns Hopkins University School of Medicine
Scientific career
InstitutionsUC San Diego School of Medicine

University of Colorado

Harvard Medical School

Robert "Chip" T. Schooley (born November 10, 1949) is an American infectious disease physician, who is the Vice Chair of Academic Affairs, Senior Director of International Initiatives, and Co-Director at the Center for Innovative Phage Applications and Therapeutics (IPATH), at the University of California San Diego School of Medicine. He is an expert in HIV and hepatitis C (HCV) infection and treatment, and in 2016, was the first physician to treat a patient in the United States with intravenous bacteriophage therapy for a systemic bacterial infection. [1]

Contents

Career

Early career

After graduating from the Johns Hopkins University School of Medicine in 1974, Schooley pursued fellowships in infectious disease at the Massachusetts General Hospital and the National Institute of Allergy and Infectious Diseases. He then focused his research on immunopathogenesis of herpesvirus infections in immunocompromised patients. In 1981, Schooley joined the faculty at Harvard Medical School as an associate professor, where he also shifted his research focus to HIV/AIDS. At this time, the first AIDS cases were identified in Boston. Schooley's research group in Boston, was one of the first groups to describe the humoral and cellular immune responses to HIV infection and he became heavily involved in the field of antiretroviral chemotherapy. [2]

HIV research

In 1990, Schooley was recruited as the head of the Division of Infectious Diseases for the Health Sciences Center at the University of Colorado, and director of the Colorado Center for AIDS Research. While at Colorado, he served as the Chair of the NIAID’s AIDS Clinical Trials Group (ACTG) which he headed from 1995 to 2002. At this time, ACTG had an annual budget of over $100 million USD. During his time as Group Chair, the ACTG expanded to include global research sites throughout Latin America, the Caribbean, South Asia and Africa, and is now the largest and most productive multinational clinical and translational research group focusing on the pathogenesis and therapy of HIV and its complications.

In 2005, he was recruited to the University of California San Diego School of Medicine, where he was the Head of the Division of Infectious Disease until 2017, and currently serves as the Vice Chair of Academic Affairs in the Department of Medicine, Senior Director of International Initiatives, and Co-Director of the Center for Innovative Phage Applications and Therapeutics.

Experience with phage therapy

In 2016, while serving as the Head of the Division of Infectious Diseases at the UC San Diego School of Medicine, Schooley was approached by his colleague, Steffanie A. Strathdee, to help save her husband's life by using bacteriophages (phages). Strathdee's husband, Tom Patterson, was suffering from a life-threatening multi-drug resistant Acinetobacter baumannii infection, that he had acquired while on vacation in Egypt. Schooley, acting as the primary infectious disease physician, along with Strathdee and a team of researchers and physicians from Texas A&M University, Adaptive Phage Therapeutics, the US Navy, UC San Diego School of Medicine, and San Diego State University, worked together to source, purify and administer phages that were active against the strain of bacteria with which Patterson was infected. Schooley was responsible for successfully navigating the Food and Drug Administration's emergency investigational new drug process, to obtain approval to administer the experimental therapy. After multiple phage cocktail administrations, provided from the partnering laboratories and companies, Patterson was cured of his infection and eventually made a full recovery. Schooley has since published a case report on his experience in treating Patterson with phage therapy, [3] and there has been a large media coverage of the story as well. [4] [5] [6] Since treating Patterson in 2016, Schooley has since been involved with the treatment of six other phage therapy patients at UC San Diego, [7] [8] and as well as consulting on a number of other phage therapy cases throughout the United States, Canada, Europe and Israel. [9] [10] In June 2018, Schooley and Strathdee were awarded a $1.2 million grant from UC San Diego Chancellor Pradeep Khosla, to help launch the Innovative Center for Phage Applications and Therapeutics (IPATH), the first phage therapy center in the United States. [11] The goal of this center is to conduct rigorous phage therapy clinical trials, that will one day lead the Food and Drug Administration to making phage therapy more widely available.

Related Research Articles

<span class="mw-page-title-main">Antibiotic</span> Antimicrobial substance active against bacteria

An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit growth of viruses are termed antiviral drugs or antivirals rather than antibiotics. They are also not effective against fungi; drugs which inhibit growth of fungi are called antifungal drugs.

<span class="mw-page-title-main">Antimicrobial resistance</span> Ability of a microbe to resist the effects of medication

Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. Protozoa evolve antiprotozoal resistance, and bacteria evolve antibiotic resistance. Bacteria that are considered extensively drug resistant (XDR) or totally drug-resistant (TDR) are sometimes referred to as a superbug. Although antimicrobial resistance is a naturally-occurring process, it is often the result of improper usage of the drugs and management of the infections.

<span class="mw-page-title-main">Bacteriophage</span> Virus that infects and replicates within bacteria

A bacteriophage, also known informally as a phage, is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν, meaning "to devour". Bacteriophages are composed of proteins that encapsulate a DNA or RNA genome, and may have structures that are either simple or elaborate. Their genomes may encode as few as four genes and as many as hundreds of genes. Phages replicate within the bacterium following the injection of their genome into its cytoplasm.

<i>Acinetobacter</i> Genus of bacteria

Acinetobacter is a genus of gram-negative bacteria belonging to the wider class of Gammaproteobacteria. Acinetobacter species are oxidase-negative, exhibit twitching motility, and occur in pairs under magnification.

<span class="mw-page-title-main">Phage therapy</span> Therapeutic use of bacteriophages to treat bacterial infections

Phage therapy, viral phage therapy, or phagotherapy is the therapeutic use of bacteriophages for the treatment of pathogenic bacterial infections. This therapeutic approach emerged at the beginning of the 20th century but was progressively replaced by the use of antibiotics in most parts of the world after the second world war. Bacteriophages, known as phages, are a form of virus that attach to bacterial cells and inject their genome into the cell. The bacteria's production of the viral genome interferes with its ability to function, halting the bacterial infection. The bacterial cell causing the infection is unable to reproduce, and instead produces additional phages. Phages are very selective in the strains of bacteria they are effective against.

<span class="mw-page-title-main">Colistin</span> Antibiotic

Colistin, also known as polymyxin E, is an antibiotic medication used as a last-resort treatment for multidrug-resistant Gram-negative infections including pneumonia. These may involve bacteria such as Pseudomonas aeruginosa, Klebsiella pneumoniae, or Acinetobacter. It comes in two forms: colistimethate sodium can be injected into a vein, injected into a muscle, or inhaled, and colistin sulfate is mainly applied to the skin or taken by mouth. Colistimethate sodium is a prodrug; it is produced by the reaction of colistin with formaldehyde and sodium bisulfite, which leads to the addition of a sulfomethyl group to the primary amines of colistin. Colistimethate sodium is less toxic than colistin when administered parenterally. In aqueous solutions it undergoes hydrolysis to form a complex mixture of partially sulfomethylated derivatives, as well as colistin. Resistance to colistin began to appear as of 2015.

<span class="mw-page-title-main">Trimethoprim/sulfamethoxazole</span> Combination of 2 antibiotic drugs

Trimethoprim/sulfamethoxazole, sold under the brand name Bactrim among others, is a fixed-dose combination antibiotic medication used to treat a variety of bacterial infections. It consists of one part trimethoprim to five parts sulfamethoxazole. It is used to treat urinary tract infections, methicillin-resistant Staphylococcus aureus (MRSA) skin infections, travelers' diarrhea, respiratory tract infections, and cholera, among others. It is used both to treat and prevent pneumocystis pneumonia and toxoplasmosis in people with HIV/AIDS and other causes of immunosuppression. It can be given by mouth or intravenously.

Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are classifications of antimicrobial agents based on their mode of action and specific to target organisms. The MDR types most threatening to public health are MDR bacteria that resist multiple antibiotics; other types include MDR viruses, parasites.

<span class="mw-page-title-main">Carbapenem</span> Class of highly effective antibiotic agents

Carbapenems are a class of very effective antibiotic agents most commonly used for the treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Similar to penicillins and cephalosporins, carbapenems are members of the beta lactam class of antibiotics, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. However, these agents individually exhibit a broader spectrum of activity compared to most cephalosporins and penicillins. Furthermore, carbapenems are typically unaffected by emerging antibiotic resistance, even to other beta-lactams.

<span class="mw-page-title-main">Rifabutin</span> Chemical compound

Rifabutin (Rfb) is an antibiotic used to treat tuberculosis and prevent and treat Mycobacterium avium complex. It is typically only used in those who cannot tolerate rifampin such as people with HIV/AIDS on antiretrovirals. For active tuberculosis it is used with other antimycobacterial medications. For latent tuberculosis it may be used by itself when the exposure was with drug-resistant TB.

<span class="mw-page-title-main">AIDS Clinical Trials Group</span>

The AIDS Clinical Trials Group network (ACTG) is one of the largest HIV clinical trials organizations in the world, playing a major role in setting standards of care for HIV infection and opportunistic diseases related to HIV and AIDS in the United States and the developing world. The ACTG is composed of, and directed by, leading clinical scientists in HIV/AIDS therapeutic research. The ACTG is funded by the Department of Health and Human Services, National Institutes of Health through the National Institute of Allergy and Infectious Diseases.

<i>Acinetobacter baumannii</i> Species of bacterium

Acinetobacter baumannii is a typically short, almost round, rod-shaped (coccobacillus) Gram-negative bacterium. It is named after the bacteriologist Paul Baumann. It can be an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived (nosocomial) infection. While other species of the genus Acinetobacter are often found in soil samples, it is almost exclusively isolated from hospital environments. Although occasionally it has been found in environmental soil and water samples, its natural habitat is still not known.

<span class="mw-page-title-main">Steffanie A. Strathdee</span> Canadian epidemiologist

Steffanie A. Strathdee is the Associate Dean of Global Health Sciences, Harold Simon Professor at the University of California San Diego School of Medicine and Co-Director at the Center for Innovative Phage Applications and Therapeutics. She has been awarded more than US$64 million in federal research grants as a principal investigator. She is known for her work on HIV research and prevention programmes in Tijuana.

Multidrug resistant Gram-negative bacteria are a type of Gram-negative bacteria with resistance to multiple antibiotics. They can cause bacteria infections that pose a serious and rapidly emerging threat for hospitalized patients and especially patients in intensive care units. Infections caused by MDR strains are correlated with increased morbidity, mortality, and prolonged hospitalization. Thus, not only do these bacteria pose a threat to global public health, but also create a significant burden to healthcare systems.

<span class="mw-page-title-main">Enzybiotics</span>

Enzybiotics are an experimental antibacterial therapy first described by Nelson, Loomis, and Fischetti. The term is derived from a combination of the words “enzyme” and “antibiotics.” Enzymes have been extensively utilized for their antibacterial and antimicrobial properties. Proteolytic enzymes called endolysins have demonstrated particular effectiveness in combating a range of bacteria and are the basis for enzybiotic research. Endolysins are derived from bacteriophages and are highly efficient at lysing bacterial cells. Enzybiotics are being researched largely to address the issue of antibiotic resistance, which has allowed for the proliferation of drug-resistant pathogens posing great risk to animal and human health across the globe.

<span class="mw-page-title-main">Plazomicin</span> Chemical compound

Plazomicin, sold under the brand name Zemdri, is an aminoglycoside antibiotic used to treat complicated urinary tract infections. As of 2019 it is recommended only for those in whom alternatives are not an option. It is given by injection into a vein.

ESKAPE is an acronym comprising the scientific names of six highly virulent and antibiotic resistant bacterial pathogens including: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. This group of Gram-positive and Gram-negative bacteria can evade or 'escape' commonly used antibiotics due to their increasing multi-drug resistance (MDR). As a result, throughout the world, they are the major cause of life-threatening nosocomial or hospital-acquired infections in immunocompromised and critically ill patients who are most at risk. P. aeruginosa and S. aureus are some of the most ubiquitous pathogens in biofilms found in healthcare. P. aeruginosa is a Gram-negative, rod-shaped bacterium, commonly found in the gut flora, soil, and water that can be spread directly or indirectly to patients in healthcare settings. The pathogen can also be spread in other locations through contamination, including surfaces, equipment, and hands. The opportunistic pathogen can cause hospitalized patients to have infections in the lungs, blood, urinary tract, and in other body regions after surgery. S. aureus is a Gram-positive, cocci-shaped bacterium, residing in the environment and on the skin and nose of many healthy individuals. The bacterium can cause skin and bone infections, pneumonia, and other types of potentially serious infections if it enters the body. S. aureus has also gained resistance to many antibiotic treatments, making healing difficult. Because of natural and unnatural selective pressures and factors, antibiotic resistance in bacteria usually emerges through genetic mutation or acquires antibiotic-resistant genes (ARGs) through horizontal gene transfer - a genetic exchange process by which antibiotic resistance can spread.

<span class="mw-page-title-main">Center for Innovative Phage Applications and Therapeutics</span> Phage therapy center in San Diego, CA, US

The Center for Innovative Phage Applications and Therapeutics (IPATH) is the first phage therapy center in North America, founded in the UC San Diego School of Medicine in June 2018, with seed funding from UC San Diego Chancellor Pradeep Khosla. The center was founded by Steffanie A. Strathdee and Robert "Chip" Schooley, both professors at UC San Diego School of Medicine. The center currently treats patients with life-threatening multi-drug resistant infections with phage therapy, on a case-by-case basis, through the Food and Drug Administration's (FDA's) compassionate use program. IPATH aims to initiate phase I/II phage therapy clinical trials, focusing on patients with cystic fibrosis and infections related to implantable hardware, such as pacemakers and prosthetic joints. The first planned clinical trial is set to look at otherwise healthy cystic fibrosis patients that are shedding Pseudomonas aeruginosa.

<span class="mw-page-title-main">Multidrug-resistant bacteria</span>

Multidrug-resistant bacteria are bacteria that are resistant to three or more classes of antimicrobial drugs. MDR bacteria have seen an increase in prevalence in recent years and pose serious risks to public health. MDR bacteria can be broken into 3 main categories: Gram-positive, Gram-negative, and other (acid-stain). These bacteria employ various adaptations to avoid or mitigate the damage done by antimicrobials. With increased access to modern medicine there has been a sharp increase in the amount of antibiotics consumed. Given the abundant use of antibiotics there has been a considerable increase in the evolution of antimicrobial resistance factors, now outpacing the development of new antibiotics.

Vincent A. Fischetti is a world renowned American microbiologist and immunologist. He is professor of and head of the Laboratory of Bacterial Pathogenesis and Immunology at Rockefeller University in New York City. His primary areas of research are bacterial pathogenesis, bacterial genetics and genomics, immunology, virology and microbiology, and mechanisms of disease. He was the first scientist to clone and sequence a surface protein on gram-positive bacteria, the M protein from S. pyogenes, and determine its unique coiled-coil structure. He also was the first use phage lysins as a therapeutic and an effective alternative to conventional antibiotics.

References

  1. UC San Diego Health, Newsroom (April 2017). "Novel Phage Therapy Saves Patient with Multidrug-Resistant Bacterial Infection". Archived from the original on May 24, 2019.
  2. Walker, BD (July 1987). "HIV-specific cytotoxic T lymphocytes in seropositive individuals". Nature. 328 (6128): 345–348. Bibcode:1987Natur.328..345W. doi:10.1038/328345a0. PMID   3496541. S2CID   4238505.
  3. Schooley, Robert (October 2017). "Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails to Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection" (PDF). Antimicrobial Agents and Chemotherapy. 61 (10). doi:10.1128/AAC.00954-17. PMC   5610518 . PMID   28807909. Archived (PDF) from the original on April 30, 2019 via American Society for Microbiology.
  4. Sockett, Liz (December 2017). "Viruses save a man from antibiotic-resistant bacteria". The Guardian. Archived from the original on March 20, 2018.
  5. "This Last-Resort Medical Treatment Offers Hope in the Fight Against Superbugs". Time. Archived from the original on November 25, 2018. Retrieved May 22, 2019.
  6. Mckenna, Maryn (June 2018). "He Was Dying. Antibiotics Weren't Working. Then Doctors Tried a Forgotten Treatment". Mother Jones. Archived from the original on May 22, 2019.
  7. LaVergne, Stephanie (March 2018). "Phage Therapy for a Multidrug-Resistant Acinetobacter baumannii Craniectomy Site Infection". Open Forum Infectious Diseases. 5 (4): ofy064. doi:10.1093/ofid/ofy064. PMC   5905571 . PMID   29687015.
  8. Aslam, Saima (April 2019). "Novel bacteriophage therapy fortreatment of left ventricular assist device infection". The Journal of Heart and Lung Transplantation. 38 (4): 475–476. doi:10.1016/j.healun.2019.01.001. PMID   30661974. S2CID   58613504.
  9. Nir-Paz, Ran (March 2019). "Successful treatment of antibiotic resistant poly-microbial bone infection with bacteriophages and antibiotics combination". Clinical Infectious Diseases. 69 (11): 2015–2018. doi:10.1093/cid/ciz222. PMID   30869755.
  10. Dedrick, RM (May 2019). "Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus". Nature Medicine. 25 (5): 730–733. doi:10.1038/s41591-019-0437-z. PMC   6557439 . PMID   31068712.
  11. "Turning a Phage". UC San Diego Health Newsroom. June 2018. Archived from the original on May 23, 2019.