||School of Medicine, Department of Anatomy, Biochemistry and Physiology
||Professor and Chair
||PhD (Ohio State School of Medicine)
||(808) 692 1442
||(808) 692 1951
||651 Ilalo St., BSB, Honolulu, HI 96813
Description of research:
There are two primary research foci in the laboratory comprising: 1) Craniofacial Morphogenesis and 2) Anatomical Imaging.
1. Craniofacial Morphogenesis: Current investigations are aimed at utilizing mouse models demonstrating heritable defects to identify important genetic components of the craniofacial complex. We have shown that the transcription factor sine oculis 2 (six2) is associated with heritable frontonasal dysplasia and renal hypoplasia utilizing the Br mutant mouse. Results have demonstrated that six2 is associated with reduced renal tubule branching and chronic renal failure in adult heterozygotes. These animals show chronic cardiovasular hypertension and decreased renal filtration ability. Similarly the fetal homozygous mice lack a presphenoid bone while medial nasal prominences show the absence of six2 expression in embryos at E11.5. Current work is aimed at physically mapping the defect as well as determining how six2 directs the development of the sphenoidal complex. A second study is examining the role of wnt9b in the development of cleft lip and palate in the CL/Fr. This collaborative study is being conducted with Dr. Kazu Nonaka at Kyushu University in Japan.
2. Computerized Modelling of the Craniofacial Region. We are working with Biomodeling Solutions to develop software capable of automatically extracting and rendering pharyngeal morphology in sleep apnea patients. The system is unique since it is implemented on an Nvidia graphics card with CUDA technology making the modeling process virtually instantaneous. Additional software is being developed to quantify pharyngeal size and shape in these patients for diagnostic and therapeutic applications.
Figure 1. WMISH of the transcription factor six2 in 3H1 +/+ (A), Br/+ (B) and Br/Br (C) mice at 11.5 days of gestation. Homozygote mutant mice
show under expression of six2 in the craniofacial region associated with the absence of a presphenoid bone in the neonate. (from: Fogelgren et al., 2008, Developmental Dynamics, 237:1767-1779.
Figure 2. Computerized modelling of the human pharynx in sleep apena patients utlizing a automatic edge detection and rendering system.
(based on Celenk et al., Journal of X-Ray Science and Technology, in press).
- Ma W, Lozanoff S. 1996. Morphological deficiency in the prenatal anterior cranial base of midfacially retrognathic mice. Journal of Anatomy, 188:547-555.
- Singh GD, McNamara JA Jr, Lozanoff S. 1997. Morphometry of the cranial base in subjects with Class III malocclusion. Journal of Dental Research 76:694-703.
- Lozanoff S. Sphenoethmoidal Growth, Malgrowth and Midfacial Profile. In: On Growth and Form: Spatio-temporal Patterning in Biology. Chapter 19. MAJ Chaplain, Dr. GD Singh and Dr. J. McLachlan
- Ma W, Lozanoff S. 2002. Differential in vitro response to epidermal growth factor by murine cranial-base chondrocytes. Archives of Oral Biology 47:155-163.
- Diewert VM, Lozanoff S. Mouse Models for Orofacial Clefting. Chapter 10. In: Etiopathogenesis of Craniosynostoses and Facial Clefting (M. Mooney and M. Siegel, eds). J. Wiley, New York 2002.
- McBratney BM, Margaryan E, Ma W, Urban Z, Lozanoff S. 2003. Frontonasal dysplasia in Br/Br mice. Anatomical Record, 271A:291-302.
- Lozanoff S, Lozanoff BK, Sora M-C, Rosenheimer J, Keep MF, Saland L, Tregear J, Jacobs J, Saiki S, Alverson D. 2003. Anatomy and the access grid: Exploiting plastinated brain sections for use in distributed medical education. Anatomical Record, 270B:30-37.
Jacobs J, Buchanan H, Lozanoff S, Lozanoff BK, Caudell T, Rosenheimer J, Saland L, Mitchell S, Saiki S, Alverson D. 2003. Integration of advanced technologies to enhance problem-based learning over distance: Project TOUCH. Anatomical Record, 270B:16-22.
- Lozanoff S, Doll, S, Hallgrimsson B, Neufeld E. 2004. Prenatal growth of the interorbital septum in Macaca mulatta. Annals of Anatomy, 185:435-442.
- Willmore K, Zelditch M, Young N, Ah-Seng A, Lozanoff S, Hallgrimsson B. 2006. Canalization and developmental stability in the Brachyrrhine mouse. Journal of Anatomy, 208:361-373.
- Sora MC, Genser-Strobl B, Radu J, Lozanoff S. 2007. Three-dimensional reconstruction of the ankle by means of ultrathin slice plastination. Clinical Anatomy, 20:196-200.
- Amella C, Cappello R, Kahl, P, Fritsch H, Lozanoff S, Sergi C. 2008. Spatial and temporal dynamics of nerve innervation during the development of the fetal human pancreas. Neuroscience, 154:477-487.
- Buchtova M, Town L, Handrigan GR, Fu K, Lozanoff S, Diewert VM, Wicking C, Richman JM. 2008 Molecular analysis of the snake dentition suggests new roles for Sonic Hedgehog in tooth initiation, morphogenesis and generational tooth formation. Development, 319:132-145.
- Fogelgren B, Kuroyama MC, McBratney-Owen B, Spence AA, Melahn LE, Anawati MK, Cabatbat C, Alarcon VB, Marikawa Y, and Lozanoff S. 2008. Misexpression of six2 is associated with heritable frontonasal dysplasia and renal hypoplasia in 3H1 Br mice. Developmental Dynamics, 237:1767-1779.
- Fogelgren B, Yang S, Sharp IC, Huckstep OJ, Ma W, Somponpun J, Carlson EC, Uyehara CFT, Lozanoff S. 2009. Deficiency in Six2 during prenatal development is associated with reduced nephron number, chronic renal failure, and hypertension in Br/+ adult mice. American Journal of Physiology (Renal Physiology) 296:1166-1178.
- Stickley CD, Hetzler RK, Kimura IF, Lozanoff S. 2009. Crural fascia and muscle origins related to medical tibial stress syndrome symptom location. Medical Science in Sports and Exercise (epub ahead of print PMID 19812520).
- Celenk M, Farrell ML, Eren H, Kumar K, Singh GD, Lozanoff S. 2009. Airway detection in cone beam images. Journal of X-Ray Science and Technology (in press).
- Wong B, Farrell ML, Freitas T, Lozanoff S. 2009. Tessellation analysis of glomerular spatial arrangement in mice with heritable renal hypoplasia. Anatomical Record (in press)