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Gillian Air  /  Sanjay Bidichandani  /  Robert Broyles
  Paul DeAngelis  /  Jay Hanas  /  Martin Levine  /  Guangpu Li 

Jialing Lin  /  Hiroyuki Matsumoto  / Blaine Mooers /  Ann Louise Olson 

Karla Rodgers  /  Robert Steinberg  /  Leon Unger  /  Paul Weigel   /  Christopher West 

Robert H. Broyles, Ph.D.
Professor
Biochemistry & Molecular Biology
Ph.D., Wake Forest, 1970

Phone: (405) 271-2227  ext. 61213
Fax:     (405) 271-3139
E-mail: robert-broyles@ouhsc.edu		  
   Mailing Address:
  940 S. L. Young Blvd., BMSB 827
  Oklahoma City, OK  73104

Broyles Lab Staff

Research Interests:  Developmental Gene Regulation

In our group of students, a few fellows and technicians, and myself, our sustaining interest has been in animal development and cellular differentiation.  The key question that has tied all of our studies together - including work on developmental changes, on cancer, and now on diseases of aging such as Parkinson's disease - is: "How are genes regulated during differentiation and development?"  The main area in which we have focused our work toward answering this question is globin gene regulation and developmental hemoglobin switching. This work has led to our discovering a repressor protein for the human adult beta-globin gene that keeps this gene repressed in embryonic cells, a nuclear form of the heavy chain of ferritin, ferritin-H (FtH).  The same protein also activates embryonic and fetal globin genes in these same cells. Since the adult beta-globin gene is the gene mutated in sickle cell disease, we propose using FtH to affect a phenotypic cure of this classic genetic disease through gene regulation therapy, i.e., by achieving a partial reversal of developmental hemoglobin switching. We have found that this therapy works as predicted when delivered to red blood cell precursor cells from pediatric sickle cell patients. Our previous work has shown that FtH also works as predicted when delivered as a transgene in an FtH transgenic mouse, and that human erythroid cells that have the beta-globin gene repressed have FtH bound to the promoter as previously mapped in vitro.

   Gene Regulation Therapy© for sickle cell disease has been patented in eleven countries.  We formed The Sickle Cell Cure Foundation, Inc (SCCF)., on July 28, 2006; and the SCCF was designated as a 501(c)(3) non-profit corporation on February 12, 2007. The SCCF recognizes sickle cell disease as the most frequently inherited genetic disease on the planet: Each month, about 1,000 babies die from SCD complications (about 350,000 annually).  SCCF has adopted a global plan for distributing the cure for SCD at low cost, in line with the recent recommendations of the World Health Organization and the WHO partnership with the March of Dimes to carryout its recommendations. You're invited to visit the SCCF website at http://www.sicklecellcurefoundation.org.  A PDF of Dr. Broyles CV is attached.

   Our other studies include environmental toxicology in which we found that a pollutant (PCBs) completely stops development of salmonid fishes at concentrations commonly found in fish breeding areas; liver cancer  which is greatly aided by a technique we developed for keeping rat liver slices alive in organotypic cultures for greater than 10 months, so that it is possible to follow the complete carcinogenesis process (including initiation, promotion and progression) in vitro and experiment very directly with ways of halting this disease; and (just begun) the use of stem cells and gene regulation to devise ways of stopping Parkinson's disease, such as chelating the excess iron that leads to substania nigral neuron death with nature's own chelator, -FtH.

 

Selected Publications -- Our best which, when taken together in chronological order, tell a story of a developing system. RHB 

 

[Search Pubmed]

Abdelmoaty H, Pye Q, Broyles RH.  Therapeutic Perspectives Involving Ferritin Heavy Chain in Parkinson’s Disease. Nova Press (in press, 2008).

 

KS, Stewart CA, Pye QN, Santambrogio P, Levi S, Arosio P, Trudel M. (2007) Ferritin heavy chain is a hemoglobin switching factor and a probable treatment for sickle cell disease and beta-thalassemias. Free Rad Biol Med 43 (Suppl): S67/#147.

 

Broyles RH, Belegu V, Roth AC, Clarkson EJ, Williamson KS, Stewart CA, Pye QN, Floyd RA, Jani K, Trudel M, Santambrogio P, Levi S, Arosio P, Cain JP. (2006) Ferritin heavy chain stimulates HbS-to-HbF switching in erythroid precursor cells from sickle cell patients. Blood 108: 790a.

 

Asada K, Kotake Y, Asada R, Saunders D, Broyles, RH, Towner RA, Fukui H, Floyd RA. (2006) LINE-1

hypomethylation in a choline-deficiency- induced liver cancer in rats: Dependence on feeding period. J. Biomed. Biotechnol. 2006/ID 17142, 1-6.

 

Broyles RH, Roth AC, Todd M, Belegu V. (2006) Nuclear reprogramming by cell fusion. In Nuclear Reprogramming: Methods and Protocols, Chap. 5 (S. Pells, ed.). Methods Molec Biol 325:47-57. Humana Press, Totowa, NJ.

 

Guo W-X, Pye QN, Williamson KS, Stewart CA, Hensley KL, Kotake Y, Floyd RA, Broyles RH. (2005) Mitochondrial dysfunction in choline deficiency-induced apoptosis in cultured rat hepatocytes. Free Radic. Biol. & Med. 39: 641-650.

 

Guo, W-X, Pye QN, Williamson KS, Stewart CA, Hensley KL, Kotake Y, Floyd RA, Broyles, R.H. (2004) Reactive oxygen species in choline deficiency-induced apoptosis in rat hepatocytes. Free Radic. Biol. & Med. 37, 1081-1089.

 

Broyles RH, Belegu V, DeWitt CR, Shah SN, Stewart CA, Pye QN, Floyd RA. (2001) Specific repression of beta-globin promoter activity by nuclear ferritin. Proc Natl Acad Sci USA 98(16):9145-50.
  
Broyles RH. (1999) Use of somatic cell fusion to reprogram globin genes. Sem Cell Devel Biol 10, 259-265.

 

Broyles RH, Blair FC, Kyker KD, Kurien BT, Stewart DR, Hala'sz H, Berg PE, Schechter A. (1995) A ferritin-like protein binds to a highly conserved CAGTGC sequence in the b-globin promoter. In Sickle Cell Disease & Thalassaemias: New Trends in Therapy (Y.Beuzard, B.Lubin, & J.Rosa, eds.), Colloque INSERM 234, 43-51. 

 

Broyles RH, Ramseyer LTH, Do TH, McBride KA, Barker JC.(1994) Hemoglobin switching in Rana/Xenopus erythroid heterokaryons.  Factors mediating the metamorphic hemoglobin switch are conserved.  Dev Genetics 15, 347-355.  

 

Smith DJ, Zhu H, Kolatkar PR, Tam L.-T, Baldwin TO, Riggs A, Roe BA, Broyles RH.  (1993) The hemoglobins of the bullfrog, Rana catesbeiana.  The cDNA-derived amino acid sequences of the alpha chain of adult hemoglobins B and C…. J Biol Chem 68, 26961-26971.

 

Ramseyer LTH, Barker-Harrel J, Smith DJ, McBride KA, Jarman RN, Broyles RH. (1989) Intracellular signals for developmental hemoglobin switching.  Dev Biol 133, 262-271.

 

Dorn AR, Broyles RH. (1982) Erythrocyte differentiation during the metamorphic hemoglobin switch of Rana catesbeiana.  Proc Natl Acad Sci USA 79, 5592-5596.

 

Broyles RH, Johnson GM, Maples PB, Kindell, G.R.  Two erythropoietic microenvironments and two larval red cell lines in bullfrog tadpoles.  Dev Biol 81,  299-314, 1981.

 

Broyles RH, Deutsch MJ. (1975) Differentiation of red blood cells in vitro.  Science 190, 471-473.

 

Broyles RH, Frieden E. (1973)  Sites of haemoglobin synthesis in amphibian tadpoles.  Nature 241, 207-209.

 

Broyles RH, Frieden E. Sites of haemoglobin synthesis in amphibian tadpoles.  Nature 241, 207-209, 1973.

 

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