Human Genetics Program

José Luis Millán, Ph.D. and young patient

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

Research Assistant Professors

Fumitoshi Irie

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

Biallelic missense variants in COG3 cause a congenital disorder of glycosylation with impairment of retrograde vesicular trafficking.

Duan R, Marafi D, Xia ZJ, Ng BG, Maroofian R, Sumya FT, Saad AK, Du H, Fatih JM, Hunter JV, Elbendary HM, Baig SM, Abdullah U, Ali Z, Efthymiou S, Murphy D, Mitani T, Withers MA, Jhangiani SN, Coban-Akdemir Z, Calame DG, Pehlivan D, Gibbs RA, Posey JE, Houlden H, Lupashin VV, Zaki MS, Freeze HH, Lupski JR

J Inherit Metab Dis 2023 Nov ;46(6):1195-1205

Beyond genetics: Deciphering the impact of missense variants in CAD deficiency.

Del Caño-Ochoa F, Ng BG, Rubio-Del-Campo A, Mahajan S, Wilson MP, Vilar M, Rymen D, Sánchez-Pintos P, Kenny J, Ley Martos M, Campos T, Wortmann SB, Freeze HH, Ramón-Maiques S

J Inherit Metab Dis 2023 Nov ;46(6):1170-1185

TMEM2 is a bona fide hyaluronidase possessing intrinsic catalytic activity.

Narita T, Tobisawa Y, Bobkov A, Jackson M, Ohyama C, Irie F, Yamaguchi Y

J Biol Chem 2023 Sep ;299(9):105120

Metabolic clogging of mannose triggers dNTP loss and genomic instability in human cancer cells.

Harada Y, Mizote Y, Suzuki T, Hirayama A, Ikeda S, Nishida M, Hiratsuka T, Ueda A, Imagawa Y, Maeda K, Ohkawa Y, Murai J, Freeze HH, Miyoshi E, Higashiyama S, Udono H, Dohmae N, Tahara H, Taniguchi N

Elife 2023 Jul 18 ;12

Tmem2 Deficiency Leads to Enamel Hypoplasia and Soft Enamel in Mouse.

Nag P, Inubushi T, Sasaki JI, Murotani T, Kusano S, Nakanishi Y, Shiraishi Y, Kurosaka H, Imazato S, Yamaguchi Y, Yamashiro T

J Dent Res 2023 Sep ;102(10):1162-1171

The Multifarious Functions of Leukotrienes in Bone Metabolism.

Amadeu de Oliveira F, Tokuhara CK, Veeriah V, Domezi JP, Santesso MR, Cestari TM, Ventura TMO, Matos AA, Dionísio T, Ferreira MR, Ortiz RC, Duarte MAH, Buzalaf MAR, Ponce JB, Sorgi CA, Faccioli LH, Buzalaf CP, de Oliveira RC

J Bone Miner Res 2023 Aug ;38(8):1135-1153

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