Neal S. Young

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Neal S. Young
Born (1947-04-13) April 13, 1947 (age 76)
New York City, New York, United States
Education Harvard College,
Johns Hopkins School of Medicine
Occupation(s)physician and researcher
Known forIntramural Research Program of the National Institutes of Health
Notable workover 500 scientific articles
SpouseGenoveffa Franchini
Children3
Awards awards and honors

Neal Stuart Young (born 1947) is an American physician and researcher, chief of the Hematology Branch of the National Institutes of Health (NIH), and Director of the Center for Human Immunology at the NIH in Bethesda, Maryland. [1] He is primarily known for his work in the pathophysiology and treatment of aplastic anemia, [2] and is also known for his contributions to the pathophysiology of parvovirus B19 infection.

Contents

Biography

Young was born in New York City on April 13, 1947. [3] He received an A.B. from Harvard College in 1967, and a M.D. from Johns Hopkins School of Medicine in 1971. His internal medicine residency was at Massachusetts General Hospital. In 1976, he completed a clinical fellowship in the Hematology-Oncology Division at Barnes Hospital, Washington University School of Medicine.

Young's entire career has been in the Intramural Research Program of the National Institutes of Health in Bethesda, Maryland. He has been Chief of the Hematology Branch of the National Heart, Lung, and Blood Institute since 1994 and was appointed Director of the Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation in 2007. [1]

He is married to Genoveffa Franchini, an expert in retroviruses and HIV in the National Cancer Institute. Their children are Andrea, a professor of physics at the University of California Santa Barbara; Massimo, vice president at Insight Investment of the Bank of New York; and Giorgio, a theoretical mathematician

Professional work

Young joined the U.S. Public Health Service in 1973 and worked at the NIH in the laboratories of Christen Anfinsen (in the immunochemistry of hemoglobin) and Arthur Nienhuis (in globin gene regulation). He directed the first multicenter clinical trial using antithymocyte globulin for the treatment of aplastic anemia in the United States. This therapy is now the standard treatment for the disease worldwide. He is credited with contributing to understanding the pathophysiology of the disease as immune-mediated and with developing immunotherapy for aplastic anemia that has dramatically improved survival rates for the disease. In the early 1980s, the disease was largely fatal with survival rates around 10% one year following the diagnosis, whereas now survival rates are 90% or better.

He also made major contributions to the understanding of parvovirus B19 infection. He identified the erythrocyte antigen P (globoside) as the cell receptor for parvovirus B19 [4] and that P antigen deficiency confers resistance to parvovirus B19 infection. Young characterized the subsequent hematologic manifestations in patients with sickle cell disease immune deficient individuals. He developed a candidate recombinant vaccine against parvovirus B19 infection.

In the 1990s, Young initiated and implemented a formal epidemiologic study of aplastic anemia in Thailand, which revealed a much higher incidence rate than in the West. [5] Coincidentally, he established a teaching program an NHLBI-sponsored teaching program in Vietnam, for which he later received a Government of Vietnam Service to the People Award. [6]

In 2005, he and his postdoctoral fellow, Rodrigo Calado, described the first mutations in the telomerase gene, TERT, in patients with aplastic anemia. Deficiency in telomerase genes causes telomere shortening, reduced hematopoietic stem cell function, and bone marrow failure. He later found that telomerase mutations also are a risk factor for acute myeloid leukemia and hepatic liver cirrhosis. In his most recent work, he has pioneered single cell genomic studies in bone marrow failure diseases, and is part of the VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory Syndrome) discovery team at NIH.

Young has published over 500 scientific articles, original research as well and reviews, which span basic molecular and cell biology, clinical research, and epidemiology and are highly cited. He was an editor for Seminars in Hematology for 20 years and has written or edited many monographs and textbooks. An article addressing the economics of scientific publishing in PLoS Medicine attracted media attention. [1] His laboratory and clinical program have trained many leaders in the hematology and bone marrow failure, who head departments in the United States, Europe, South America, and Asia. His Winner’s Curse essay of 2008 [7] was an influential contribution to the literature on scientific publishing; in 2023, he was a Visiting Fellow at New College, Oxford, to address language issues in science from a philosophic perspective.

Awards and honors

Selected publications

Books

Review Articles

Recent Original Research

Related Research Articles

<i>Parvoviridae</i> Family of viruses

Parvoviruses are a family of animal viruses that constitute the family Parvoviridae. They have linear, single-stranded DNA (ssDNA) genomes that typically contain two genes encoding for a replication initiator protein, called NS1, and the protein the viral capsid is made of. The coding portion of the genome is flanked by telomeres at each end that form into hairpin loops that are important during replication. Parvovirus virions are small compared to most viruses, at 23–28 nanometers in diameter, and contain the genome enclosed in an icosahedral capsid that has a rugged surface.

Aplastic anemia (AA) is a severe hematologic condition in which the body fails to make blood cells in sufficient numbers. Aplastic anemia is associated with cancer and various cancer syndromes. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood cells, white blood cells, and platelets.

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

Erythema infectiosum, fifth disease, or slapped cheek syndrome is one of several possible manifestations of infection by parvovirus B19. Fifth disease typically presents as a rash and is more common in children. While parvovirus B19 can affect humans of all ages, only two out of ten individuals will present with physical symptoms.

<span class="mw-page-title-main">Paroxysmal nocturnal hemoglobinuria</span> Medical condition

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occurs due to deficiency of the red blood cell surface protein DAF, which normally inhibits such immune reactions. Since the complement cascade attacks the red blood cells within the blood vessels of the circulatory system, the red blood cell destruction (hemolysis) is considered an intravascular hemolytic anemia. There is ongoing research into other key features of the disease, such as the high incidence of venous blood clot formation. Research suggests that PNH thrombosis is caused by both the absence of GPI-anchored complement regulatory proteins on PNH platelets and the excessive consumption of nitric oxide (NO).

Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (thrombocytes). Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine. The risk is especially high in cytotoxic chemotherapy for leukemia. In the case of non-small-cell lung cancer, myelosuppression predisposition was shown to be modulated by enhancer mutations.

<span class="mw-page-title-main">Parvovirus B19</span> Human virus that infects RBC precursors

Human parvovirus B19, generally referred to as B19 virus(B19V),parvovirus B19 or sometimes erythrovirus B19, is a known human virus in the family Parvoviridae, genus Erythroparvovirus; it measures only 23–26 nm in diameter. Human parvovirus b19 is a below-species classification of Erythroparvovirus primate1. The name is derived from Latin parvum, meaning small, reflecting the fact that B19 ranks among the smallest DNA viruses. B19 virus is most known for causing disease in the pediatric population; however, it can also affect adults. It is the classic cause of the childhood rash called fifth disease or erythema infectiosum, or "slapped cheek syndrome". The name comes from it being the fifth in a list of historical classifications of common skin rash illnesses in children.

<i>Chicken anemia virus</i> Species of virus

Chicken anemia virus, or CAV, is currently a member of the Anelloviridae family which is found worldwide. The virus only affects chickens. CAV is a non-enveloped icosahedral single stranded DNA virus, which causes bone marrow atrophy, anemia, and severe immunosuppression. Clinical signs of CAV infection are predominantly found in young chicks due to vertical transmission from the breeder hens whose maternal antibodies have not yet formed following exposure. Clinical disease is rare today because of the widespread practice of vaccinating breeders, but the subclinical form of the disease—which normally affects birds more than two weeks of age following horizontal transmission of the virus via the fecal–oral route—is ubiquitous. The virus is very resistant in the environment, making elimination very difficult.

<span class="mw-page-title-main">Dyskeratosis congenita</span> Medical condition

Dyskeratosis congenita (DKC), also known as Zinsser-Engman-Cole syndrome, is a rare progressive congenital disorder with a highly variable phenotype. The entity was classically defined by the triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa, and MDS/AML, but these components do not always occur. DKC is characterized by short telomeres. Some of the manifestations resemble premature ageing and cognitive impairment can be a feature. The disease initially mainly affects the skin, but a major consequence is progressive bone marrow failure which occurs in over 80%, causing early mortality.

<span class="mw-page-title-main">Pure red cell aplasia</span> Medical condition

Pure red cell aplasia (PRCA) or erythroblastopenia refers to a type of aplastic anemia affecting the precursors to red blood cells but usually not to white blood cells. In PRCA, the bone marrow ceases to produce red blood cells. There are multiple etiologies that can cause PRCA. The condition has been first described by Paul Kaznelson in 1922.

Transient erythroblastopenia of childhood (TEC) is a slowly developing anemia of early childhood characterized by gradual onset of pallor.

Reticulocytopenia is the medical term for an abnormal decrease in circulating red blood cell precursors (reticulocytes) that can lead to anemia due to resulting low red blood cell (erythrocyte) production. Reticulocytopenia may be an isolated finding or it may not be associated with abnormalities in other hematopoietic cell lineages such as those that produce white blood cells (leukocytes) or platelets (thrombocytes), a decrease in all three of these lineages is referred to as pancytopenia.

Myelophthisic anemia is a severe type of anemia found in some people with diseases that affect the bone marrow. Myelophthisis refers to the displacement of hemopoietic bone-marrow tissue by fibrosis, tumors, or granulomas. The word comes from the roots myelo-, which refers to bone marrow, and phthysis, shrinkage or atrophy.

Pearson syndrome is a mitochondrial disease characterized by sideroblastic anemia and exocrine pancreas dysfunction. Other clinical features are failure to thrive, pancreatic fibrosis with insulin-dependent diabetes and exocrine pancreatic deficiency, muscle and neurologic impairment, and, frequently, early death. It is usually fatal in infancy. The few patients who survive into adulthood often develop symptoms of Kearns–Sayre syndrome. It is caused by a deletion in mitochondrial DNA. Pearson syndrome is very rare: fewer than a hundred cases have been reported in medical literature worldwide.

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

Eltrombopag, sold under the brand name Promacta among others, is a medication used to treat thrombocytopenia and severe aplastic anemia. Eltrombopag is sold under the brand name Revolade outside the US and is marketed by Novartis. It is a thrombopoietin receptor agonist. It is taken by mouth.

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

H/ACA ribonucleoprotein complex subunit 4 is a protein that in humans is encoded by the gene DKC1.

<span class="mw-page-title-main">Revesz syndrome</span> Medical condition

Revesz syndrome is a fatal disease that causes exudative retinopathy and bone marrow failure. Other symptoms include severe aplastic anemia, intrauterine growth retardation, fine sparse hair, fine reticulate skin pigmentation, ataxia due to cerebellar hypoplasia, and cerebral calcifications. Its effects are similar to that of Hoyeraal-Hreidarsson syndrome. It is a variant of dyskeratosis congenita.

The stem cell theory of aging postulates that the aging process is the result of the inability of various types of stem cells to continue to replenish the tissues of an organism with functional differentiated cells capable of maintaining that tissue's original function. Damage and error accumulation in genetic material is always a problem for systems regardless of the age. The number of stem cells in young people is very much higher than older people and thus creates a better and more efficient replacement mechanism in the young contrary to the old. In other words, aging is not a matter of the increase in damage, but a matter of failure to replace it due to a decreased number of stem cells. Stem cells decrease in number and tend to lose the ability to differentiate into progenies or lymphoid lineages and myeloid lineages.

<span class="mw-page-title-main">Hoyeraal–Hreidarsson syndrome</span> Medical condition

Hoyeraal–Hreidasson syndrome is a very rare multisystem X-linked recessive disorder characterized by excessively short telomeres and is considered a severe form of dyskeratosis congenita. Being an X-linked disorder, Hoyeraal–Hreidasson syndrome primarily affects males. Patients typically present in early childhood with cerebellar hypoplasia, immunodeficiency, progressive bone marrow failure, and intrauterine growth restriction. The primary cause of death in Hoyeraal–Hreidasson syndrome is bone marrow failure, but mortality from cancer and pulmonary fibrosis is also significant.

GATA2 deficiency is a grouping of several disorders caused by common defect, namely, familial or sporadic inactivating mutations in one of the two parental GATA2 genes. Being the gene haploinsufficient, mutations that cause a reduction in the cellular levels of the gene's product, GATA2, are autosomal dominant. The GATA2 protein is a transcription factor critical for the embryonic development, maintenance, and functionality of blood-forming, lymphatic-forming, and other tissue-forming stem cells. In consequence of these mutations, cellular levels of GATA2 are deficient and individuals develop over time hematological, immunological, lymphatic, or other presentations that may begin as apparently benign abnormalities but commonly progress to severe organ failure, opportunistic infections, virus infection-induced cancers, the myelodysplastic syndrome, and/or leukemia. GATA2 deficiency is a life-threatening and precancerous condition.

References

  1. 1 2 3 Web Page at NIH
  2. ↑ NS Young, RT Calado, P Scheinberg "Current concepts in the pathophysiology and treatment of aplastic anemia" Blood Oct. 2006 108(8):2509-2519 NCBI link cited 19 times according to Google Scholar
  3. ↑ LC Authority file
  4. ↑ KE Brown, SM Anderson, NS Young "Erythrocyte P antigen: cellular receptor for B19 parvovirus" Science 1 October 1993: Vol. 262 no. 5130 pp. 114-117 cited 744 times according to Google Scholar
  5. ↑ The epidemiology of aplastic anemia in Thailand
  6. ↑ Aplastic Anemia and Bone Marrow Failure Syndromes: a Journey
  7. ↑ https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0050201
  8. ↑ WorldCat item reference
  9. ↑ item reference
  10. ↑ Calado RT, Young NS. Telomere diseases. N Engl J Med. 2009 Dec 10;361(24):2353-65
  11. ↑ Young NS. Aplastic Anemia. N Engl J Med. 2018 Oct 25;379(17):1643-1656
  12. ↑ Mustjoki S, Young NS. Somatic Mutations in "Benign" Disease. N Engl J Med. 2021 May 27;384(21):2039-2052
  13. ↑ Danazol Treatment for Telomere Diseases. N Engl J Med. 2016 May 19;374(20):1922-31.
  14. ↑ Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia. N Engl J Med. 2017 Apr 20;376(16):1540-1550.
  15. ↑ Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease. N Engl J Med. 2020 Dec 31;383(27):2628-2638.
  16. ↑ Long-term outcomes in patients with severe aplastic anemia treated with immunosuppression and eltrombopag: a phase 2 study. Blood. 2022 Jan 6;139(1):34-43
  17. ↑ Efficacy of JAK1/2 inhibition in murine immune bone marrow failure. Blood. 2023 Jan 5;141(1):72-89.
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