Amy Proal

Last updated
Amy Proal
Education Georgetown University
Murdoch University
Known for Long COVID research
Scientific career
FieldsMicrobiology
InstitutionsAutoimmunity Research Foundation
PolyBio Research Foundation
Thesis Autoimmune disease re-examined in light of metagenomic concepts  (2012)
Doctoral advisors Trevor Marshall
Cassandra Berry
Douglas Eagles

Amy Proal is an American microbiologist who studies the effects of bacterial, fungal, and viral pathogens on human health at the molecular level. She is one of the founders of PolyBio Research Foundation, a company investigating the basis of chronic infection-associated illnesses, and currently serves on the company's board of directors. [1] She has recently been noted for her work investigating the causes of long covid. [2] [3] [4]

Contents

Education

Proal received her Bachelor of Science in biology from Georgetown University in 2005 and later obtained her PhD in microbiology at Murdoch University in 2012. Her graduate work focused on characterizing dysregulated pathways in the context of autoimmune disease and potential avenues of treatment. Her doctoral thesis was titled "Autoimmune disease re-examined in light of metagenomic concepts". [5]

Career

Proal's decision to pursue a career in microbiology was motivated by personal experience with severe and repeated infections as a young child and later during her undergraduate studies when she was diagnosed with chronic fatigue syndrome (ME/CFS). [6] After completing her PhD, she continued to explore the link between persistent viral pathogens in the human body and chronic illness. She became a member of the research team at the Autoimmunity Research Foundation, a California-based nonprofit, where she has published papers on autoimmunity in the context of the human microbiome, [7] the role of host-microbe interaction in microbiome dysbiosis and inflammation, [8] and the relationship between the pathogens driving ME/CFS and the human microbiome. [9]

She is one of the founding members and current president/chief scientific officer of PolyBio Research Foundation, a 501(c)3 dedicated to investigating the molecular mechanisms underlying infection-associated chronic illnesses including ME/CFS, Lyme disease, and more recently Long COVID, as well as their effect on immunity, human metabolism, and inflammatory response.

Proal spearheaded the launch of the Long COVID Research Consortium in September 2022, [10] a collaboration between scientists at premier institutions across the country, to study the fundamental causes of Long Covid.

Discoveries

An idea inspired from her personal experience with ME/CFS and severe infections during the early stages of childhood, Proal began to explore pathogenesis as a driver of autoimmunity. In her paper titled "The human microbiome and autoimmunity", [11] Proal discusses how the accumulation of pathogens in the human microbiome perturb gene transcription, translation, and metabolic process. The paper also proposes that autoimmune diseases may be the result of the inheritance of a specific microbiome composition rather than "Mendelian inheritance of genetic abnormalities”. [11]

Proal has also authored several chapters of books written for the J.Craig Venter Institute. One of the chapters she wrote in the book titled "Infection and Autoimmunity" [12] states that intracellular microbes tamper with key metabolic pathways by gradually dysregulating gene expression. She explains that the expression of the Vitamin D receptor is altered in many inflammatory conditions since Vitamin D is an immunosuppressive steroid which dampens the innate immune response, allowing pathogens to proliferate more easily.

More recently, she has been launching research efforts to study the aftereffects of Long COVID. She and her research team have recently documented in the article "Long COVID or post-acute sequelae of COVID-19 (PASC): an overview of biological factors that may contribute to persistent symptoms" [13] some of the factors that may give rise to Long COVID symptoms, including Sars-Cov-2 injury to one or multiple organs, reservoirs of the virus in tissues, and an viral induced immunosuppressive environment.

Notable works

Related Research Articles

<span class="mw-page-title-main">Autoimmunity</span> Immune response against an organisms own healthy cells

In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". Prominent examples include celiac disease, diabetes mellitus type 1, Henoch–Schönlein purpura (HSP), systemic lupus erythematosus (SLE), Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis (RA), ankylosing spondylitis, polymyositis (PM), dermatomyositis (DM), and multiple sclerosis (MS). Autoimmune diseases are very often treated with steroids.

<span class="mw-page-title-main">Human microbiome</span> Microorganisms in or on human skin and biofluids

The human microbiome is the aggregate of all microbiota that reside on or within human tissues and biofluids along with the corresponding anatomical sites in which they reside, including the skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, biliary tract, and gastrointestinal tract. Types of human microbiota include bacteria, archaea, fungi, protists, and viruses. Though micro-animals can also live on the human body, they are typically excluded from this definition. In the context of genomics, the term human microbiome is sometimes used to refer to the collective genomes of resident microorganisms; however, the term human metagenome has the same meaning.

In medicine, the hygiene hypothesis states that early childhood exposure to particular microorganisms protects against allergies by strengthening the immune system. In particular, a lack of such exposure is thought to lead to poor immune tolerance. The time period for exposure begins before birth and ends at school age.

<span class="mw-page-title-main">Asymptomatic carrier</span> Organism which has become infected with a pathogen but displays no symptoms

An asymptomatic carrier is a person or other organism that has become infected with a pathogen, but shows no signs or symptoms.

<span class="mw-page-title-main">Liver disease</span> Medical condition

Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.

A sequela is a pathological condition resulting from a disease, injury, therapy, or other trauma. Derived from the Latin word meaning "sequel", it is used in the medical field to mean a complication or condition following a prior illness or disease.

<span class="mw-page-title-main">Helminthic therapy</span> Deliberate infestation with parasitic worms

Helminthic therapy, an experimental type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the eggs of a helminth. Helminths are parasitic worms such as hookworms, whipworms, and threadworms that have evolved to live within a host organism on which they rely for nutrients. These worms are members of two phyla: nematodes, which are primarily used in human helminthic therapy, and flat worms (trematodes).

<span class="mw-page-title-main">Gut microbiota</span> Community of microorganisms in the gut

Gut microbiota, gut microbiome, or gut flora, are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut microbiota. The gut is the main location of the human microbiome. The gut microbiota has broad impacts, including effects on colonization, resistance to pathogens, maintaining the intestinal epithelium, metabolizing dietary and pharmaceutical compounds, controlling immune function, and even behavior through the gut–brain axis.

Dysbiosis is characterized by a disruption to the microbiome resulting in an imbalance in the microbiota, changes in their functional composition and metabolic activities, or a shift in their local distribution. For example, a part of the human microbiota such as the skin flora, gut flora, or vaginal flora, can become deranged, with normally dominating species underrepresented and normally outcompeted or contained species increasing to fill the void. Dysbiosis is most commonly reported as a condition in the gastrointestinal tract.

<span class="mw-page-title-main">Microbial symbiosis and immunity</span>

Long-term close-knit interactions between symbiotic microbes and their host can alter host immune system responses to other microorganisms, including pathogens, and are required to maintain proper homeostasis. The immune system is a host defense system consisting of anatomical physical barriers as well as physiological and cellular responses, which protect the host against harmful microorganisms while limiting host responses to harmless symbionts. Humans are home to 1013 to 1014 bacteria, roughly equivalent to the number of human cells, and while these bacteria can be pathogenic to their host most of them are mutually beneficial to both the host and bacteria.

<span class="mw-page-title-main">Microbiota</span> Community of microorganisms

Microbiota are the range of microorganisms that may be commensal, mutualistic, or pathogenic found in and on all multicellular organisms, including plants. Microbiota include bacteria, archaea, protists, fungi, and viruses, and have been found to be crucial for immunologic, hormonal, and metabolic homeostasis of their host.

<span class="mw-page-title-main">Autoimmune disease</span> Disorders of adaptive immune system

An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated that there are more than 80 recognized autoimmune diseases, with recent scientific evidence suggesting the existence of potentially more than 100 distinct conditions. Nearly any body part can be involved.

<span class="mw-page-title-main">Myalgic encephalomyelitis/chronic fatigue syndrome</span> Medical condition

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating long-term medical condition. People with ME/CFS experience lengthy flare-ups of the illness following relatively minor physical or mental activity. This is known as post-exertional malaise (PEM) and is the hallmark symptom of the illness. Other core symptoms are a greatly reduced ability to do tasks that were previously routine, severe fatigue, and sleep disturbances. The baseline fatigue in ME/CFS does not improve much with rest. Orthostatic intolerance, memory and concentration problems, and chronic pain are common. About a quarter of people with ME/CFS are severely affected and unable to leave their bed or home.

The altered Schaedler flora (ASF) is a community of eight bacterial species: two lactobacilli, one Bacteroides, one spiral bacterium of the Flexistipes genus, and four extremely oxygen sensitive (EOS) fusiform-shaped species. The bacteria are selected for their dominance and persistence in the normal microflora of mice, and for their ability to be isolated and grown in laboratory settings. Germ-free animals, mainly mice, are colonized with ASF for the purpose of studying the gastrointestinal (GI) tract. Intestinal mutualistic bacteria play an important role in affecting gene expression of the GI tract, immune responses, nutrient absorption, and pathogen resistance. The standardized microbial cocktail enabled the controlled study of microbe and host interactions, role of microbes, pathogen effects, and intestinal immunity and disease association, such as cancer, inflammatory bowel disease, diabetes, and other inflammatory or autoimmune diseases. Also, compared to germfree animals, ASF mice have fully developed immune system, resistance to opportunistic pathogens, and normal GI function and health, and are a great representation of normal mice.

Metatranscriptomics is the set of techniques used to study gene expression of microbes within natural environments, i.e., the metatranscriptome.

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

Pharmacomicrobiomics, proposed by Prof. Marco Candela for the ERC-2009-StG project call, and publicly coined for the first time in 2010 by Rizkallah et al., is defined as the effect of microbiome variations on drug disposition, action, and toxicity. Pharmacomicrobiomics is concerned with the interaction between xenobiotics, or foreign compounds, and the gut microbiome. It is estimated that over 100 trillion prokaryotes representing more than 1000 species reside in the gut. Within the gut, microbes help modulate developmental, immunological and nutrition host functions. The aggregate genome of microbes extends the metabolic capabilities of humans, allowing them to capture nutrients from diverse sources. Namely, through the secretion of enzymes that assist in the metabolism of chemicals foreign to the body, modification of liver and intestinal enzymes, and modulation of the expression of human metabolic genes, microbes can significantly impact the ingestion of xenobiotics.

Long COVID or long-haul COVID is a group of health problems persisting or developing after an initial period of COVID-19 infection. Symptoms can last weeks, months or years and are often debilitating. The World Health Organization defines long COVID as starting three months after the initial COVID-19 infection, but other agencies define it as starting at four weeks after the initial infection.

Post-acute infection syndromes (PAISs) or post-active phase of infection syndromes are a group of medical conditions characterized by chronic illness triggered by an infection. They are sometimes referred to as infection-associated chronic illnesses as well. While it is commonly assumed that people either recover or die from infections, illness is a possible outcome as well. Examples include long COVID, chronic fatigue syndrome (ME/CFS), and post-Ebola virus syndrome. Common symptoms include post-exertional malaise (PEM), severe fatigue, neurocognitive symptoms, flu-like symptoms, and pain. The pathology of most of these conditions is not understood and management is generally symptomatic.

Carmen Scheibenbogen is a German immunologist who is the acting director of the Institute for Medical Immunology of the Charité university hospital in Berlin. She specialises in hematology, oncology and immunology. She leads the Outpatient Clinic for Immunodeficiency and the Fatigue Centre at the Charité hospital. She is one of the few doctors specialised in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in Germany, and also researches long COVID.

References

  1. "PolyBio Research Foundation - Science in Action!". PolyBio Research Foundation. Retrieved 2023-11-28.
  2. Steenhuysen, Julie (September 8, 2022). "Top scientists join forces to study leading theory behind long COVID". Reuters. Retrieved 13 December 2023.
  3. Hart, Robert (September 8, 2022). "Billionaire-Backed Group Steps Up Hunt For Long Covid Treatment". Forbes. Retrieved 13 December 2023.
  4. Belluz, Julia (April 14, 2021). "Scientists haven't figured out long Covid. Here are 5 of their best hypotheses". Vox. Retrieved 13 December 2023.
  5. 1 2 Proal, Amy. ""Autoimmune disease re-examined in light of metagenomic concepts"". researchportal.murdoch.edu.au. Retrieved 2023-11-28.
  6. "Reactivated Viruses Causing Chronic Fatigue & Long-Haul COVID-19". Mitchell Medical Group. 2021-09-01. Retrieved 2023-11-29.
  7. Proal, Amy D.; Marshall, Trevor G. (2018-06-26). "Re-framing the Theory of Autoimmunity in the Era of the Microbiome: Persistent Pathogens, Autoantibodies, and Molecular Mimicry". Discovery Medicine. 25 (140): 299–308. PMID   30021103.
  8. 1 2 Proal, Amy D.; Lindseth, Inge A.; Marshall, Trevor G. (2017-01-19). "Microbe-Microbe and Host-Microbe Interactions Drive Microbiome Dysbiosis and Inflammatory Processes". Discovery Medicine. 23 (124): 51–60. PMID   28245427.
  9. 1 2 Proal, Amy; Marshall, Trevor (2018-12-04). "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity". Frontiers in Pediatrics. 6: 373. doi: 10.3389/fped.2018.00373 . ISSN   2296-2360. PMC   6288442 . PMID   30564562.
  10. "New research initiative will focus on root causes of long COVID". The Los Angeles Times. September 7, 2022. Retrieved 13 December 2023.
  11. 1 2 Proal, Amy D.; Albert, Paul J.; Marshall, Trevor G. (March 2013). "The human microbiome and autoimmunity". Current Opinion in Rheumatology. 25 (2): 234–240. doi:10.1097/BOR.0b013e32835cedbf. ISSN   1040-8711. PMID   23370376. S2CID   6726537.
  12. 1 2 Proal, Amy D.; Albert, Paul J.; Marshall, Trevor G. (2015), "Infection, Autoimmunity, and Vitamin D", Infection and Autoimmunity, Elsevier, pp. 163–182, doi:10.1016/b978-0-444-63269-2.00007-6, ISBN   978-0-444-63269-2 , retrieved 2023-11-29
  13. 1 2 Proal, Amy D.; VanElzakker, Michael B. (2021-06-23). "Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms". Frontiers in Microbiology. 12. doi: 10.3389/fmicb.2021.698169 . ISSN   1664-302X. PMC   8260991 . PMID   34248921.
  14. Proal, Amy D.; VanElzakker, Michael B. (January 2021). "Pathogens Hijack Host Cell Metabolism: Intracellular Infection as a Driver of the Warburg Effect in Cancer and Other Chronic Inflammatory Conditions". Immunometabolism. 3 (1). doi: 10.20900/immunometab20210003 . ISSN   2633-0407.