Gene effects
Most genetic disorders are present from birth and are quite rare, often affecting only one person in every several thousand or million.
While some of these genetic diseases are well known, such as sickle cell anemia and cystic fibrosis, others are so rare that there is only one affected person in the world. Whether a genetic disease affects thousands or just one person, there are many challenges for patients, their families, and caregivers, including the time it takes for many patients to get a correct diagnosis.
Director's statement
Our focus is on the discovery of new genetic disorders and improving our understanding of those we already know. Using zebrafish, mouse models, patient cells and stem cell technologies, we are probing the pathological mechanisms of genetic disorders to address unanswered questions. Our fundamental research has led to clinically useful diagnostic tests and novel therapies for patients. Strong patient and advocacy relations serve as a foundation for our goal to shed light on the obscure paths of genetic disorders and provide solid information and guidance.
– Hudson Freeze, Ph.D., Program Director
Appointments
Program Director
Primary Appointments
Duc Dong, Ph.D.
José Luis Millán, Ph.D.
Evan Snyder, M.D., Ph.D.
Yu Yamaguchi, M.D., Ph.D.
Publications
Inhibition of Tissue-Nonspecific Alkaline Phosphatase Attenuates Ectopic Mineralization in the Abcc6(-/-) Mouse Model of PXE but Not in the Enpp1 Mutant Mouse Models of GACI.
Li Q, Huang J, Pinkerton AB, Millan JL, van Zelst BD, Levine MA, Sundberg JP, Uitto J
J Invest Dermatol 2019 Feb ;139(2):360-368
A mammalian homolog of the zebrafish transmembrane protein 2 (TMEM2) is the long-sought-after cell-surface hyaluronidase.
Yamamoto H, Tobisawa Y, Inubushi T, Irie F, Ohyama C, Yamaguchi Y
J Biol Chem 2017 May 5 ;292(18):7304-7313
A Recurrent De Novo Heterozygous COG4 Substitution Leads to Saul-Wilson Syndrome, Disrupted Vesicular Trafficking, and Altered Proteoglycan Glycosylation.
Ferreira CR, Xia ZJ, Clément A, Parry DA, Davids M, Taylan F, Sharma P, Turgeon CT, Blanco-Sánchez B, Ng BG, Logan CV, Wolfe LA, Solomon BD, Cho MT, Douglas G, Carvalho DR, Bratke H, Haug MG, Phillips JB, Wegner J, Tiemeyer M, Aoki K, Undiagnosed Diseases Network, Scottish Genome Partnership, Nordgren A, Hammarsjö A, Duker AL, Rohena L, Hove HB, Ek J, Adams D, Tifft CJ, Onyekweli T, Weixel T, Macnamara E, Radtke K, Powis Z, Earl D, Gabriel M, Russi AHS, Brick L, Kozenko M, Tham E, Raymond KM, Phillips JA 3rd, Tiller GE, Wilson WG, Hamid R, Malicdan MCV, Nishimura G, Grigelioniene G, Jackson A, Westerfield M, Bober MB, Gahl WA, Freeze HH
Am J Hum Genet 2018 Oct 4 ;103(4):553-567
Elevated oxysterol and N-palmitoyl-O-phosphocholineserine levels in congenital disorders of glycosylation.
Dang Do AN, Chang IJ, Jiang X, Wolfe LA, Ng BG, Lam C, Schnur RE, Allis K, Hansikova H, Ondruskova N, O'Connor SD, Sanchez-Valle A, Vollo A, Wang RY, Wolfenson Z, Perreault J, Ory DS, Freeze HH, Merritt JL, Porter FD
J Inherit Metab Dis 2023 Mar ;46(2):326-334
Gene Therapy Using Recombinant AAV Type 8 Vector Encoding TNAP-D(10) Improves the Skeletal Phenotypes in Murine Models of Osteomalacia.
Amadeu de Oliveira F, Mohamed FF, Kinoshita Y, Narisawa S, Farquharson C, Miyake K, Foster BL, Millan JL
JBMR Plus 2023 Jan ;7(1):e10709
Increased PHOSPHO1 and alkaline phosphatase expression during the anabolic bone response to intermittent parathyroid hormone delivery.
Houston DA, Stephen LA, Jayash SN, Myers K, Little K, Hopkinson M, Pitsillides AA, MacRae VE, Millan JL, Staines KA, Farquharson C
Cell Biochem Funct 2023 Mar ;41(2):189-201
Regenerative failure of intrahepatic biliary cells in Alagille syndrome rescued by elevated Jagged/Notch/Sox9 signaling.
Zhao C, Matalonga J, Lancman JJ, Liu L, Xiao C, Kumar S, Gates KP, He J, Graves A, Huisken J, Azuma M, Lu Z, Chen C, Ding BS, Dong PDS
Proc Natl Acad Sci U S A 2022 Dec 13 ;119(50):e2201097119
GLUT1 is a highly efficient L-fucose transporter.
Ng BG, Sosicka P, Xia Z, Freeze HH
J Biol Chem 2023 Jan ;299(1):102738
COG4 mutation in Saul-Wilson syndrome selectively affects secretion of proteins involved in chondrogenesis in chondrocyte-like cells.
Xia ZJ, Mahajan S, Paul Daniel EJ, Ng BG, Saraswat M, Campos AR, Murad R, He M, Freeze HH
Front Cell Dev Biol 2022 ;10:979096
