José Luis Millán, Ph.D.

José Luis Millán, Ph.D. headshot

José Luis Millán, Ph.D.

Fax: (858) 646-3195

José Luis Millán's Research Focus

Bone Mineralization Disorders, Colorectal Cancer, Testicular Cancer, Heart Disease, Peripheral Vascular Disease, Arthritis, Crohn’s Disease (Colitis), Metabolic Syndrome, Cardiovascular Diseases, Inherited Disorders
Cardiovascular Biology, Extracellular Matrix, Protein Structure-Function Relationships, Disease Therapies
Cardiovascular System, Musculoskeletal System, Vasculature

The Millán laboratory works on understanding the mechanisms that control normal skeletal and dental mineralization and elucidating the pathophysiological abnormalities that lead to heritable soft bones conditions such as Hypophosphatasia (HPP) and to soft-tissue calcification, including vascular calcification, that is a hallmark in patients affected by a variety of rare genetic diseases as well as in chronic kidney disease. Dr. Millán’s research has already contributed to the implementation of a novel therapy for HPP, a genetic disease caused by deficiency in tissue-nonspecific alkaline phosphatase (TNAP) function, that leads to accumulation in the extracellular space of inorganic pyrophosphate (PPi), a potent inhibitor of mineralization. HPP is characterized by defective mineralization of bones (rickets or osteomalacia), and teeth that display a lack of acellular cementum, hypomineralized dentin and enamel, and periodontal defects. Dr. Millán’s team has demonstrated the effectiveness of enzyme replacement therapy using mineral-targeted recombinant TNAP (asfotase alfa) to prevent the skeletal and dental defects in the TNAP knockout mouse model of infantile HPP. This therapy was approved in 2015 for the treatment of patients with pediatric-onset HPP.

Current efforts, in collaboration with Professor Miyake’s group in Japan (, focus on developing gene therapy as an alternative approach to treat HPP. Dr. Millán’s group has also identified key pathophysiological changes that lead to calcification of the arteries in animal models of generalized arterial calcification of infancy, pseudoxanthoma elasticum and related genetic diseases as well as in animal models of chronic kidney disease. His group, in collaboration with scientists at the Conrad Prebys Center for Chemical Genomics at Sanford Burnham Prebys, has developed proprietary compounds able to ameliorate the soft-tissue calcification in these conditions and clinical trials are now underway using these first-in-class small molecule inhibitors.

José Luis Millán's Bio

After receiving his early training in clinical chemistry/biochemistry at the University of Buenos Aires, Argentina, Dr. Millán first joined the La Jolla Cancer Research Foundation (LJCRF) in 1977, the predecessor of Sanford Burnham Prebys, as a trainee in clinical enzymology. He completed his Ph.D. studies in Medical Biochemistry at the University of Umeå, Sweden and after post-doctoral stints in Copenhagen and LJCRF he was appointed to the faculty at SBP in 1986. He served as Professor of Medical Genetics in the Department of Medical Biosciences at his alma mater, Umeå University, Sweden, from 1995-2000. He was appointed Sanford Investigator at the Sanford Children’s Health Research Center at Sanford Burnham Prebys in 2008.


Honors and Recognition

2018: ASBMR Lawrence G. Raisz Award for Pre-clinical Research.
2001: Gold Medal of the Royal Academy of Medicine and Surgery, Murcia, Spain
1992: Honorary title of AcadémicoCorresponsal at the Royal Academy of Medicine and Surgery, Murcia, Spain.


Other Affiliations

Member, Scientific Advisory Board, Soft Bones

Human Genetics Accessory


Inhibition of tissue-nonspecific alkaline phosphatase protects against medial arterial calcification and improves survival probability in the CKD-MBD mouse model.

Tani T, Fujiwara M, Orimo H, Shimizu A, Narisawa S, Pinkerton AB, Millán JL, Tsuruoka S

J Pathol 2020 Jan ;250(1):30-41

Visualization of Mineral-Targeted Alkaline Phosphatase Binding to Sites of Calcification In Vivo.

Amadeu de Oliveira F, Narisawa S, Bottini M, Millán JL

J Bone Miner Res 2020 Sep ;35(9):1765-1771

Gene Therapy Using Adeno-Associated Virus Serotype 8 Encoding TNAP-D(10) Improves the Skeletal and Dentoalveolar Phenotypes in Alpl(-/-) Mice.

Kinoshita Y, Mohamed FF, Amadeu de Oliveira F, Narisawa S, Miyake K, Foster BL, Millán JL

J Bone Miner Res 2021 Sep ;36(9):1835-1849

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Glycoproteomic profile of human tissue-nonspecific alkaline phosphatase expressed in osteoblasts.

Atanasova D, Mirgorodskaya E, Moparthi L, Koch S, Haarhaus M, Narisawa S, Millán JL, Landberg E, Magnusson P

JBMR Plus 2024 Feb ;8(2):ziae006

Differential effects of the lipidic and ionic microenvironment on NPP1's phosphohydrolase and phosphodiesterase activities.

Andrilli LHS, Sebinelli HG, Cominal JG, Bolean M, Hayann L, Millán JL, Ramos AP, Ciancaglini P

Biochim Biophys Acta Biomembr 2024 Apr ;1866(4):184292

Do Media Extracellular Vesicles and Extracellular Vesicles Bound to the Extracellular Matrix Represent Distinct Types of Vesicles?

Mebarek S, Buchet R, Pikula S, Strzelecka-Kiliszek A, Brizuela L, Corti G, Collacchi F, Anghieri G, Magrini A, Ciancaglini P, Millan JL, Davies O, Bottini M

Biomolecules 2023 Dec 28 ;14(1)

Annexin A5 stabilizes matrix vesicle-biomimetic lipid membranes: unravelling a new role of annexins in calcification.

Ferreira CR, Cruz MAE, Bolean M, Andrilli LHDS, Millan JL, Ramos AP, Bottini M, Ciancaglini P

Eur Biophys J 2023 Nov ;52(8):721-733

Evidence that pyrophosphate acts as an extracellular signalling molecule to exert direct functional effects in primary cultures of osteoblasts and osteoclasts.

Bourne LE, Davies BK, Millan JL, Arnett TR, Wheeler-Jones CPD, Keen JAC, Roberts SJ, Orriss IR

Bone 2023 Nov ;176:116868

Dentoalveolar Alterations in an Adenine-Induced Chronic Kidney Disease Mouse Model.

Mohamed FF, Amadeu de Oliveira F, Kinoshita Y, Yalamanchili RR, Eltilib LA, Andras NL, Narisawa S, Tani T, Chu EY, Millán JL, Foster BL

J Bone Miner Res 2023 Aug ;38(8):1192-1207

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