Research and Education Opportunity Queensland- Ochsner Research and Education Opportunity

Bedside to Basic Science 1) Unique, difficult case for which no consensus report or algorithm exists 2) Scientific team approach to medical care 3) Brings basic science into the clinical practice 4) Preparation for precision medicine and goal of physicians being physician- scientists 5) Potentially benefits students, residents, fellows, staff, institution and patient.

Team Queensland- Ochsner student Fellow ** Resident optional Staff Physician of patient Ochsner expert Scientists internal and external Supported by Research: Drs. J. Alam and R. Re, and Education: Dr. L Seoane

Process Identification of case Review of case: Pertinent history and physical findings, laboratory, and as appropriate review of X-rays with radiology and tissue with pathologists Background: Basic science related to case Hypothesis Further testing Short Phenotypic and Genetic description Presentation to Queensland piers and team Publication: Abstract and/or Publication

Cases that Improved My Clinical Skills OI gene mutation, Type 1 collagen and Osteoporosis HIGH BMD, gene mutation LRP5, wnt and beta- catenin, bone formation Tumoral Calcinosis GALNT-3 mutation and phosphorus metabolism and vascular calcification Hypercalcemia and Liver Cirrhosis

Proving the Concept Hypercalcemia and liver cirrhosis Corrected calcium higher than ionized calcium, PTH suppressed and other tests Nl. 5 cases identified. Epic Slicer/ dicer to identify more cases Multifactorial: immobilization, cholestasis An O-Glycosylation of Fibronectin Mediates Hepatic Osteodystrophy Through α4β1 Integrin Sens C ……Nakchbandi I J Bone Miner Res. 2017 32(1):70-81

Fibronectin Synthesis in liver and secreted and polymerizes in the bone and/or bone marrow. Master switch for the matrix Important for matrix structure and signals by binding integrins Important for embryology and vascular development and epithelial to mesenchymal transition Oncofetal- fibronectin elevated in embryo and with cirrhosis

Studies Retrospective Histopathological Study to determine what cell in the liver is responsible for synthesis of FN and OFF in various liver dx. Collaborators: Drs. I. Nakchbandi, A Cohen, G. Galliano, plus team Prospective Trial evaluating histopathology with quantitative score of various liver diseases and serum measurement of OFF, FN, and markers of bone formation and resorption. Clinical study to evaluate mechanism of hypercalcemia in ESLD

Scientific Questions Hypercalcemia and cirrhosis: What is the relationship? Is it more common with cholestasis? Is there an inverse relationship between OFF and osteocalcin? Does OFF or fibronectin come from the stellate cell or hepatocyte or some other cell of liver? Is OFF an autocrine factor, paracrine factor or hormone? Do different hepatic diseases or normal hepatic tissue show differences in OFF and FN ? Do the levels vary with HCC. Is there a correlation with blood levels and osteocalcin levels? Fibrosis is related to collagen types 1 and 3, TGF-B, CCN2, Fibronectin, fibronectin polymerization, integrin, beta catenin,