Publications by authors named "Betty Lam"

Purpose: To evaluate the dynamic transitions in diabetic retinopathy (DR) severity over time and associated risk factors in an Asian population with diabetes.

Design: Longitudinal cohort study METHODS: We analyzed data from 9481 adults in the Singapore Integrated Diabetic Retinopathy Screening Program (2010-2015) with linkage to death registry. A multistate Markov model adjusted for age, sex, systolic blood pressure (SBP), diabetes duration, HbA1c, and body mass index (BMI) was applied to estimate annual transition probabilities between four DR states (no, mild, moderate, and severe/proliferative) and death, and the mean sojourn time in each state.

View Article and Find Full Text PDF

WRN helicase is a promising target for treatment of cancers with microsatellite instability (MSI) due to its essential role in resolving deleterious non-canonical DNA structures that accumulate in cells with faulty mismatch repair mechanisms. Currently there are no approved drugs directly targeting human DNA or RNA helicases, in part owing to the challenging nature of developing potent and selective compounds to this class of proteins. Here we describe the chemoproteomics-enabled discovery of a clinical-stage, covalent allosteric inhibitor of WRN, VVD-133214.

View Article and Find Full Text PDF

Background: Persistent sinus tachycardia (ST) is frequently encountered during pregnancy and peripartum period and its etiology often remains elusive. We sought to examine the possible association between unexplained persistent ST and obstetric outcomes.

Methods: A case control study was conducted using chart review of women admitted in labor to one of 7 hospitals of Northwell Health between January 2015 to June 2021.

View Article and Find Full Text PDF

Electronic medical records are increasingly being leveraged to improve the efficiency and effectiveness of clinical trials. Reporting safety data and adhering to follow-up schedules are two challenges faced by study centers conducting a large number of clinical trials led by a single principal investigator. The Lenox Hill Electrophysiology Research Department collaborated with Northwell Health's informatics department to develop a live query accessing both inpatient and outpatient data.

View Article and Find Full Text PDF

The orphan G-protein-coupled receptor GPR139 is highly expressed in the habenula, a small brain nucleus that has been linked to depression, schizophrenia (SCZ), and substance-use disorder. High-throughput screening and a medicinal chemistry structure-activity relationship strategy identified a novel series of potent and selective benzotriazinone-based GPR139 agonists. Herein, we describe the chemistry optimization that led to the discovery and validation of multiple potent and selective in vivo GPR139 agonist tool compounds, including our clinical candidate TAK-041, also known as NBI-1065846 (compound ).

View Article and Find Full Text PDF

Using structure-based drug design, we identified a novel series of 5,6-dihydroimidazolo[1,5-f]pteridine PLK1 inhibitors. Rational improvements to compounds of this class resulted in single-digit nanomolar enzyme and cellular activity against PLK1, and oral bioavailability. Compound 1 exhibits >7 fold induction of phosphorylated Histone H3 and is efficacious in an in vivo HT-29 tumor xenograft model.

View Article and Find Full Text PDF

Spleen Tyrosine Kinase (SYK) is a non-receptor cytoplasmic tyrosine kinase that is primarily expressed in hematopoietic cells. SYK is a key mediator for a variety of inflammatory cells, including B cells, mast cells, macrophages and neutrophils and therefore, an attractive approach for treatment of both inflammatory diseases and oncology indications. Using in house co-crystal structure information, and structure-based drug design, we designed and optimized a novel series of heteroaromatic pyrrolidinone SYK inhibitors resulting in the selection of the development candidate TAK-659.

View Article and Find Full Text PDF

Using structure-based drug design, we identified and optimized a novel series of pyrimidodiazepinone PLK1 inhibitors resulting in the selection of the development candidate TAK-960. TAK-960 is currently undergoing Phase I evaluation in adult patients with advanced solid malignancies.

View Article and Find Full Text PDF

Dipeptidyl peptidase IV (DPP-4) inhibitors have been shown to enhance GLP-1 levels and thereby improve hyperglycemia in type II diabetes. From a small fragment hit, using structure-based design, we have discovered a new class of non-covalent, potent and selective DPP-4 inhibitors.

View Article and Find Full Text PDF