Showing papers by "Jerry S.H. Lee published in 2021"

BloodPAC Data Commons for Liquid Biopsy Data

Abstract: PURPOSEThe Blood Profiling Atlas in Cancer (BloodPAC) Data Commons (BPDC) is being developed and is operated by the public-private BloodPAC Consortium to support the liquid biopsy community. It is ...

A field guide to cultivating computational biology

Abstract: Evolving in sync with the computation revolution over the past 30 years, computational biology has emerged as a mature scientific field. While the field has made major contributions toward improving scientific knowledge and human health, individual computational biology practitioners at various institutions often languish in career development. As optimistic biologists passionate about the future of our field, we propose solutions for both eager and reluctant individual scientists, institutions, publishers, funding agencies, and educators to fully embrace computational biology. We believe that in order to pave the way for the next generation of discoveries, we need to improve recognition for computational biologists and better align pathways of career success with pathways of scientific progress. With 10 outlined steps, we call on all adjacent fields to move away from the traditional individual, single-discipline investigator research model and embrace multidisciplinary, data-driven, team science.

Potential association between public medical insurance, waitlist mortality, and utilization of living donor liver transplantation: An analysis of the Scientific Registry of Transplant Recipients

Abstract: BACKGROUND The Affordable Care Act (ACA) and subsequent Medicaid expansion has increased utilization of public health insurance. Living donor liver transplantation (LDLT) increases access to transplant and is associated with improved survival but consistently represents < 5% of LT in the United States. STUDY DESIGN National registry data were analyzed to evaluate the impact of insurance payor on waitlist mortality and LDLT rates at LDLT centers since implementation of the ACA. RESULTS Public insurance [Medicare RR 1.18 (1.13-1.22) P < .001, Medicaid RR 1.22 (1.18-1.27) P < .001], Latino ethnicity (P < .001), and lower education level (P = .02) were associated with increased waitlist mortality at LDLT centers. LDLT recipients were more likely to have private insurance (70.4% vs. 59.4% DDLT, P < .001), be Caucasian (92.1% vs. 83% DDLT, P < .001), and have post-secondary education (66.8% vs. 54.1% DDLT, P < .001). Despite 78% of LDLT centers being located in states with Medicaid expansion, there was no change in LDLT utilization among recipients with Medicaid (P = .196) or Medicare (P = .273). CONCLUSION Despite Medicaid expansion, registry data suggests that patients with public medical insurance may experience higher waitlist mortality and underutilize LDLT at centers offering LDLT. It is possible that Medicaid expansion has not increased access to LDLT.

Paradoxical androgen receptor regulation by small molecule enantiomers.

Abstract: Small molecules that target the androgen receptor (AR) are the mainstay of therapy for lethal castration-resistant prostate cancer (CRPC), yet existing drugs lose their efficacy during continued treatment. This evolution of resistance is due to heterogenous mechanisms which include AR mutations causing the identical drug to activate instead of inhibit the receptor. Understanding in molecular detail the paradoxical phenomenon wherein an AR antagonist is transformed into an agonist by structural mutations in the target receptor is thus of paramount importance. Herein, we describe a reciprocal paradox: opposing antagonist and agonist AR regulation determined uniquely by enantiomeric forms of the same drug structure. The antiandrogen BMS-641988, which has (R)-chirality at C-5 encompasses a previously uncharacterized (S)-stereoisomer that is, surprisingly, a potent agonist of AR, as demonstrated by transcriptional assays supported by cell imaging studies. This duality was reproduced in a series of novel compounds derived from the BMS-641988 scaffold. Coupled with in silico modeling studies, the results inform an AR model that explains the switch from potent antagonist to high-affinity agonist in terms of C-5 substituent steric interactions with helix 12 of the ligand binding site. They imply strategies to overcome AR drug resistance and demonstrate that insufficient enantiopurity in this class of AR antagonist can confound efforts to correlate structure with function.

Evaluating the impact of ideation and actualization of multidisciplinary research

Abstract: Global events in the past year has made prescient a long-standing debate on the definition and suitability of impact and novelty as criteria for publication in selective journals. Reflecting on this issue, Prof Andrea Armani and Prof Jerry Lee argue that rigour and reproducibility is, in fact, more crucial. Global events in the past year has made prescient a long-standing debate on the definition and suitability of impact and novelty as criteria for publication in selective journals. Reflecting on this issue, Prof Andrea Armani and Prof Jerry Lee argue that rigour and reproducibility is, in fact, more crucial.

A field guide to cultivating computational biology.

Abstract: Biomedical research centers can empower basic discovery and novel therapeutic strategies by leveraging their large-scale datasets from experiments and patients. This data, together with new technologies to create and analyze it, has ushered in an era of data-driven discovery which requires moving beyond the traditional individual, single-discipline investigator research model. This interdisciplinary niche is where computational biology thrives. It has matured over the past three decades and made major contributions to scientific knowledge and human health, yet researchers in the field often languish in career advancement, publication, and grant review. We propose solutions for individual scientists, institutions, journal publishers, funding agencies, and educators.