Yusuf A. Hannun

Last updated
Yusuf A. Hannun
Born
Yusuf Awni Hannun

September 21, 1955
Saudi Arabia
OccupationMedical researcher
Known forSphingolipid signaling and metabolism

Yusuf A. Hannun is an American molecular biologist, biochemist, and clinician. He is known for the discovery that sphingolipids have signaling functions.

Contents

Early life

Yusuf Awni Hannun was born in Saudi Arabia of Palestinian parents, Mrs. Aida Ashur-Hannun and Dr. Awni Hannun. He received his early education in Beirut at the International College and earned a Bachelor of Science at the American University of Beirut in 1977. [1] Following his undergraduate degree, Hannun continued at the American University of Beirut, obtaining an MD with distinction in 1981 and completing his internship and a residency in internal medicine [2]

Discovery of Sphingolipid Signaling

In 1983, Hannun left Lebanon to take up specialty training at Duke University with a fellowship in hematology and oncology as well as undergoing post-doctoral training in Biochemistry under Professor Robert Bell. [1] It was during this time that Hannun made the initial discovery that protein kinase C was inhibited by sphingosine, [2] showing a bioactive effect for a sphingolipid for the first time and suggesting that "a role for sphingolipids in transmembrane signaling may emerge". [2] Prior to this discovery, sphingolipids had primarily been thought to be inert, structural components of cell membranes. Subsequent work by Hannun and his laboratory demonstrated the turnover of sphingolipids in response to cell stimuli, [3] [4] analogous to phosphoinositide turnover, and the linking of sphingolipids, most notably ceramide, to biologies such as cell death, growth arrest, and differentiation. [3] [4] [5] [6] These early studies by Hannun and his colleagues ushered in a period of broader investigation on sphingolipid metabolism and function.

Subsequent career

In 1998, Hannun moved to the Medical University of South Carolina (MUSC) to be Chair of Biochemistry and Molecular Biology, holding the Ralph F. Hirschmann Chair of Biomedical Research, and serving as Deputy Director of the Hollings Cancer Center. While at MUSC the center was noted by the National Cancer Institute as NCI-designated. At that time there were only sixty such designated centers in the United States.

In 2012, Hannun was recruited to be Director of the Cancer Center and Vice Dean for Cancer Medicine at Stony Brook University. He is also co-director of the Kavita and Lalit Bahl Center for Metabolomics and Imaging, [7] [8] a major program focused on the study of lipids, metabolism, and imaging in Cancer Biology and Therapeutics. [9] Under Hannun's leadership, cancer research and care at Stony Brook has expanded, including the establishment of a new department of bioinformatics to use computer technology to collect and analyze biological data. This culminated in the opening of the Medical and Research Translation (MART) facility in 2019, which enables scientists and clinicians to work in close proximity, to help advance cancer research and rapidly translate basic research findings into new clinical tools and therapies. [10]

Research Contributions, Honors, and Awards

In the field of bioactive sphingolipids, Hannun has contributed over 500 academic research articles and reviews, and published a number of books. In 2004, he was elected as a fellow in the American Association for the Advancement of Science. [11] In 2006, he was given the South Carolina Governor's award for scientific research. [12] In 2011, he was awarded the ASBMB Avanti award for excellence in research. [13] [14] The contributions of Hannun and his wife Lina M. Obeid to sphingolipid research were recognized by a Lifetime Achievement Award at the 16th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases - the first time that it was given as a joint award. [15]

Personal life

While at the American University of Beirut, Hannun met his wife Lina M. Obeid, a fellow physician scientist and biomedical researcher who also made seminal contributions to the sphingolipid field. Their triplet children, [16] Reem, Marya, and Awni, have all found careers in research. [17] [18] [19] Obeid passed away in November 2019 from complications of lung cancer. [20]

Related Research Articles

Sphingolipid

Sphingolipids are a class of lipids containing a backbone of sphingoid bases, a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sphinx because of their enigmatic nature. These compounds play important roles in signal transduction and cell recognition. Sphingolipidoses, or disorders of sphingolipid metabolism, have particular impact on neural tissue. A sphingolipid with an R group consisting of a hydrogen atom only is a ceramide. Other common R groups include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids.

Sphingomyelin

Sphingomyelin is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphocholine and ceramide, or a phosphoethanolamine head group; therefore, sphingomyelins can also be classified as sphingophospholipids. In humans, SPH represents ~85% of all sphingolipids, and typically make up 10–20 mol % of plasma membrane lipids.

Fumonisin B1 Chemical compound

Fumonisin B1 is the most prevalent member of a family of toxins, known as fumonisins, produced by several species of Fusarium molds, such as Fusarium verticillioides, which occur mainly in maize (corn), wheat and other cereals. Fumonisin B1 contamination of maize has been reported worldwide at mg/kg levels. Human exposure occurs at levels of micrograms to milligrams per day and is greatest in regions where maize products are the dietary staple.

Ceramide Family of waxy lipid molecules

Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer. Contrary to previous assumptions that ceramides and other sphingolipids found in cell membrane were purely supporting structural elements, ceramide can participate in a variety of cellular signaling: examples include regulating differentiation, proliferation, and programmed cell death (PCD) of cells.

Lipid signaling

Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses. Lipid signaling is thought to be qualitatively different from other classical signaling paradigms because lipids can freely diffuse through membranes. One consequence of this is that lipid messengers cannot be stored in vesicles prior to release and so are often biosynthesized "on demand" at their intended site of action. As such, many lipid signaling molecules cannot circulate freely in solution but, rather, exist bound to special carrier proteins in serum.

Sphingomyelin phosphodiesterase Class of enzymes

Sphingomyelin phosphodiesterase is a hydrolase enzyme that is involved in sphingolipid metabolism reactions. SMase is a member of the DNase I superfamily of enzymes and is responsible for breaking sphingomyelin (SM) down into phosphocholine and ceramide. The activation of SMase has been suggested as a major route for the production of ceramide in response to cellular stresses.

Ceramidase is an enzyme which cleaves fatty acids from ceramide, producing sphingosine (SPH) which in turn is phosphorylated by a sphingosine kinase to form sphingosine-1-phosphate (S1P).

In enzymology, a ceramide kinase, also abbreviated as CERK, is an enzyme that catalyzes the chemical reaction:

UGCG Protein-coding gene in the species Homo sapiens

Ceramide glucosyltransferase is an enzyme that in humans is encoded by the UGCG gene.

ASAH2

Neutral ceramidase is an enzyme that in humans is encoded by the ASAH2 gene.

UGT8

2-hydroxyacylsphingosine 1-beta-galactosyltransferase is an enzyme that in humans is encoded by the UGT8 gene.

Lactosylceramide

The Lactosylceramides, also known as LacCer, are a class of glycosphingolipids composed of a variable hydrophobic ceramide lipid and a hydrophilic sugar moiety. Lactosylceramides are found in microdomains on the plasma layers of numerous cells. Moreover, they are a type of ceramide including lactose, which is an example of a globoside.

Ceramide synthase 3

Ceramide synthase 3 (CersS3), also known as longevity assurance homologue 3, is an enzyme that is encoded in humans by the CERS3 gene.

Ceramide synthase 5 (CerS5) is the enzyme encoded in humans by the CERS5 gene.

Ceramide-activated protein phosphatases (CAPPs) are a group of enzymes that are activated by the lipid second messenger ceramide. Known CAPPs include members of the protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) families. CAPPs are a subset of intracellular serine/threonine phosphatases. Each CAPP consists of a catalytic subunit which confers phosphatase activity and a regulatory subunit which confers substrate specificity. CAPP involvement has been implicated in glycogen metabolism, apoptotic pathways related to cancer and other cellular pathways related to Alzheimer’s disease.

Sarah Spiegel is professor and chair of the Department of Biochemistry and Molecular Biology at Virginia Commonwealth University (VCU). In the mid-1990s she discovered the sphingosine-1-phosphate molecule, a lipid which has been identified as a signaler for the spread of cancer, inflammation, and cardiovascular disease. She runs the Spiegel-Milstien Lab, which studies S1P, at VCU.

Iwao Ojima

Iwao Ojima is a Japanese-American chemist and university distinguished professor at the State University of New York at Stony Brook. He has been widely recognized for his seminal contributions to a range of chemical research at the multifaceted interfaces of chemical synthesis and life sciences. As rare accomplishments, he has received four National Awards from the American Chemical Society in four different fields of research. He is also serving as the director of the Institute of Chemical Biology and Drug Discovery (ICB&DD), as well as the president of the Stony Brook Chapter of the National Academy of Inventors.

The 1-deoxysphingolipids (1-deoxySLs) are an atypical and recently discovered class of sphingolipids (SLs). They are formed during the nove synthesis pathway and their essential C1-OH deficit causes the malfunctions of the following transformations to achieve complex sphingolipids. In general, sphingolipids are formed during a reaction that is catalyzed by the SPT enzyme (serine-palmitoyltransferase) where the condensation of serine and palmitoyl-CoA takes place. The origin of this rare sphingolipid, though, is due to a defect of the SPT which can also use alanine or glycine. This change is what forms the 1-deoxySL.

Lina M. Obeid was an American physician and cancer researcher.

Maurizio Del Poeta is a Distinguished Professor and American lipid, infectious diseases, and cancer researcher focusing on novel anti-fungal drug discovery and lipid-mediated fungal pathogenesis.

References

  1. 1 2 "Yusuf Hannun". Honorary Doctorates, American University of Beirut. Retrieved 2020-05-19.
  2. 1 2 3 Yusuf A. Hannun, Carson R. Loomis, Alfred A. Merril Jr, and Robert M. Bell "Sphingosine inhibition of protein kinase C activity and of phorbol dibutyrate binding in vitro and in human platelets" J. Biol. Chem., vol. 261, issue 27, 1986, p. 12604-9. Accessed 19 May 2020.
  3. 1 2 T. Okazaki, R. Bell. and Y.A. Hannun "Sphingomyelin turnover induced by vitamin D3 in HL-60 cells: Role in cell differentiation" J. Biol. Chem., vol. 264, issue 32, 1989, p. 19076-80. Accessed 19 May 2020.
  4. 1 2 3. M-Y. Kim, C. Linardic, L. Obeid, and Y.A. Hannun "Identification of Sphingomyelin Turnover as an Effector Mechanism for the Action of TNF-alpha and Interferon-gamma: Specific Role in Cell Differentiation" J. Biol. Chem., vol. 266, issue 1, 1991, p. 484-89. Accessed 19 May 2020.
  5. ↑ Lina M. Obeid, Corrine M. Linardic, Linda A. Karolak, and Yusuf A. Hannun "Programmed cell death induced by ceramide" Science, vol. 259, issue 5102, 1993, p. 1769-1771. Accessed 18 May 2020.
  6. ↑ S. Jayadev, B. Liu, A.E. Bielawska, J.Y. Lee, F. Nazaire, MYu. Pushkareva, L.M. Obeid, and Y.A. Hannun "Role for ceramide in cell cycle arrest" J. Biol. Chem., vol. 270, issue 5, 1995, p. 2047-2052. Accessed 19 May 2020.
  7. ↑ Ricks, Delthia (November 30, 2016). "Cancer center opening at Stony Brook". Newsday. Retrieved 2020-01-11.
  8. ↑ "The Kavita and Lalit Bahl Center for Metabolomics and Imaging". Youtube. Retrieved 2020-05-19.
  9. ↑ Avila, Joseph De (November 13, 2006). "Family History Inspires Cancer Lab". Wall Street Journal. Retrieved 2020-01-11.
  10. ↑ "The Future of Cancer Care and Research". Stony Brook University News. November 16, 2018. Retrieved 2020-06-09.
  11. ↑ "2004 AAAS Fellows annual report" (PDF). AAAS. Retrieved 2020-06-12.
  12. ↑ Abole, Cindy. "Hannun receives governor's award in science". MUSC. Retrieved 2020-06-12.
  13. ↑ "South Carolina researcher wins Avanti Award in Lipids". Eurekalert. Retrieved 2020-06-12.
  14. ↑ "Avanti Award in Lipids". ASBMB. Retrieved 2020-06-12.
  15. ↑ "Dynamic Duo: Cancer Researchers Receive Lifetime Achievement Award". Stony Brook Cancer Center. Retrieved 2020-05-19.
  16. ↑ McCurdy, Layton (May 29, 2012). "Biochemistry, Molecular Biology chair named". Medical University of South Carolina. Retrieved 2020-01-11.
  17. ↑ "Bio - Reem A Hannun". NASA Science and Exploration Directorate. Retrieved 2020-01-11.
  18. ↑ "Marya Hannun". Georgetown University Faculty Directory. Retrieved 2020-01-11.
  19. ↑ "Awni Hannun". Stanford University. Retrieved 2020-01-11.
  20. ↑ Dunaief, Daniel. "Lina Obeid, Renowned Award-Winning SBU Scientist". TBR News Media. Retrieved 2020-01-11.
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