DESCRIPTION (provided by applicant) Funds are requested to purchase an Illumina HiSeq 3000 Sequencer for the Genome Sequencing Facility (GSF) of Greehey Children's Cancer Research Institute (GCCRI) at the University of Texas Health Science Center at San Antonio (UTHSCSA). At the present time, high throughput sequencing is conducted on a heavily utilized Illumina HiSeq 2000 sequencer that was purchased in December 2010, and there were no other publicly accessible high-throughput NGS platforms within UTHSCSA and surrounding San Antonio institutions.

This Phase 2, double-blind, randomized, placebo-controlled, multicenter study, with an open-label LTSE, will evaluate the effect of Obeticholic Acid, and the subsequent addition of statin therapy, on lipoprotein metabolism in subjects with NASH with fibrosis stage 1 to 4, but no evidence of hepatic decompensation

Applied Research

This Phase 3b, double-blind, randomized, placebo-controlled, multicenter study is being undertaken at up to 170 sites internationally to evaluate the effect of OCA on clinical outcomes in 350 subjects with PBC. The study will include a screening period of up to 8 weeks, requiring two clinic visits. Eligible participants will be randomly allocated (1:1) to treatment with either OCA 5 mg or matching placebo tablets, taken orally once daily. Randomization will be stratified by standard treatment with UDCA (yes/no) and baseline liver function.

Non-Alcoholic Steatohepatitis (NASH) is a growing epidemic in the western world due to the contemporary eating habits and life styles.NASH can lead to cirrhosis, hepatic carcinoma and other liver complications. There are currently some treatments available. The only definitive way of detecting NASH in patients with advanced liver disease is by liver biopsy. However, liver biopsy has disadvantages, such as sampling errors, chance of complications and does not lend itself to following up after treatment.

Factors in the tumor microenvironment promote immunosuppression that permits tumor escape from immune destruction. Our data show that tumor PD-L1 (CD274, B7-H1) is a major regulator of tumor inflammatory lymphocyte (TIL) infiltrate. PD-L1 is widely expressed in many tumors and is the target of two successful new cancer immunotherapy approaches, but is a poor predictor of treatment efficacy.

T lymphocytes are critical mediators of immunity; however they are continuously lost for a variety of reasons throughout life, and therefore must be replaced. Generation of new T cells is the function of the thymus, and the unique stromal microenvironment in the thymus directs T cell development and the selection of self- tolerant, self-restricted T cell population. Unfortunately, the thymus undergoes a precipitous age-induced atrophy resulting in reduced naÔve T cell production.

Basic Research

The goals of this program are: Project 1) Biology of the human lung mucosa in aging and tuberculosis; Project 2) Biology of alveolar macrophages in aging and tuberculosis; Project 3) Defining age-associated immune correlates of susceptibility to M. tuberculosis; and Project 4) Defining immune correlates of susceptibility to M. tuberculosis infection in the elderly" Txbiomed Project: 4696