patrick c walsh

INTRODUCTION AND OBJECTIVEIn 1985, there were 22 female urologists in the United States. The same year, the first female resident at the Brady Urological Institute began her final year of training. Over thirty-five years later, despite women’s increasing participation in medicine, women still represent a small fraction of all practicing urologists. This project therefore sought to understand the complexities and nuances of navigating the field of urology as a woman, through oral histories conducted with eight out of the sixteen women who trained at the Brady Urological Institute at Johns Hopkins University from 1980 to 2022. As the first residency in urology in the United States and a leader in urological treatment and research, the Brady Urological Institute at Johns Hopkins has been at the forefront of many developments in the field. By understanding the experiences of women urologists both at the Brady and more …

Background Although men of African ancestry (AA) have the highest mortality rate from prostate cancer (PCa), relatively little is known about the germline variants that are associated with PCa risk in AA men. The goal of this study is to systematically evaluate rare, recurrent nonsynonymous variants across the exome for their association with PCa in AA men. Methods Whole exome sequencing (WES) of germline DNA in two AA PCa patient cohorts of Johns Hopkins Hospital (N = 960) and Wayne State University (N = 747) was performed. All nonsynonymous variants present in both case cohorts, with a carrier rate between 0.5% and 1%, were identified. Their carrier rates were compared with rates from 8128 African/African American (AFR) control subjects from The Genome Aggregation Database (gnomAD) using Fisher's exact test. Significant variants, defined as false discovery rate (FDR) adjusted p‐value ≤ …

A rare African ancestry–specific germline deletion variant in HOXB13 (X285K, rs77179853) was recently reported in Martinican men with early-onset prostate cancer. Given the role of HOXB13 germline variation in prostate cancer, we investigated the association between HOXB13 X285K and prostate cancer risk in a large sample of 22 361 African ancestry men, including 11 688 prostate cancer cases. The risk allele was present only in men of West African ancestry, with an allele frequency in men that ranged from 0.40% in Ghana and 0.31% in Nigeria to 0% in Uganda and South Africa, with a range of frequencies in men with admixed African ancestry from North America and Europe (0–0.26%). HOXB13 X285K was associated with 2.4-fold increased odds of prostate cancer (95% confidence interval [CI] = 1.5-3.9, p = 2 × 10−4), with greater risk observed for more aggressive and advanced disease (Gleason ≥8 …

BackgroundRecently, a novel HOXB13 variant (X285K) was observed in men of African descent with prostate cancer (PCa) in Martinique. Little is known about this or other variants in HOXB13 which may play a role in PCa susceptibility in African-American (AA) men.MethodsWe sequenced HOXB13 in an AA population of 1048 men undergoing surgical treatment for PCa at Johns Hopkins Hospital.ResultsSeven non-synonymous germline variants were observed in the patient population. While six of these variants were seen only once, X285K was found in eight patients. In a case–case analysis, we find that carriers of this latter variant are at increased risk of clinically significant PCa (1.2% carrier rate in Gleason Score ≥7 PCa vs. 0% in Gleason Score <7 PCa, odds ratio, OR = inf; 95% Confidence Interval, 95%CI:1.05-inf, P = 0.028), as well as PCa with early age at diagnosis (2.4% carrier rate in patients <50 …

2021 Joseph A. Smith, Jr. Mentorship lecture: Discovery — Johns Hopkins University Skip to main navigation Skip to search Skip to main content Johns Hopkins University Home Johns Hopkins University Logo Home Profiles Research units Research output Search by expertise, name or affiliation 2021 Joseph A. Smith, Jr. Mentorship lecture: Discovery Patrick C. Walsh School of Medicine Research output: Contribution to journal › Article › peer-review Overview Original language English (US) Pages (from-to) 15-17 Number of pages 3 Journal Urologic Oncology: Seminars and Original Investigations Volume 40 Issue number 2 DOIs https://doi.org/10.1016/j.urolonc.2021.12.007 State Published - Feb 2022 Keywords Francis D. Moore James Buchanan Brady Urological Institute Mentoring Prostate cancer Urology residency training ASJC Scopus subject areas Oncology Urology Access to Document 10.1016/j.urolonc.…

PurposeOur goal was to evaluate the comparative effectiveness of robot-assisted laparoscopic prostatectomy (RALP) and open radical prostatectomy (ORP) in a multicenter study.Materials and MethodsWe evaluated men with localized prostate cancer at 11 high-volume academic medical centers in the United States from the PROST-QA (2003–2006) and the PROST-QA/RP2 cohorts (2010–2013) with a pre-specified goal of comparing RALP (549) and ORP (545). We measured longitudinal patient-reported health-related quality of life (HRQOL) at pre-treatment and at 2, 6, 12, and 24 months, and pathological and perioperative outcomes/complications.ResultsDemographics, cancer characteristics, and margin status were similar between surgical approaches. ORP subjects were more likely to undergo lymphadenectomy (89% vs 47%; p <0.01) and nerve sparing (94% vs 89%; p <0.01). RALP vs ORP subjects …

We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins and phosphosites, prioritizes copy number drivers, and highlights an oncogenic role for RNA processing genes. Proteomic investigation of mutual exclusivity between FAT1 truncating mutations and 11q13.3 amplifications reveals dysregulated actin dynamics as a common functional consequence. Phosphoproteomics characterizes two modes of EGFR activation, suggesting a new strategy to stratify HNSCCs based on EGFR ligand abundance for effective treatment with inhibitory EGFR monoclonal antibodies. Widespread deletion of immune modulatory genes accounts for low immune infiltration in immune-cold tumors, whereas concordant upregulation of multiple immune checkpoint proteins may underlie …

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient survival. Toward understanding the underlying molecular alterations that drive PDAC oncogenesis, we conducted comprehensive proteogenomic analysis of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 normal pancreatic ductal tissues. Proteomic, phosphoproteomic, and glycoproteomic analyses were used to characterize proteins and their modifications. In addition, whole-genome sequencing, whole-exome sequencing, methylation, RNA sequencing (RNA-seq), and microRNA sequencing (miRNA-seq) were performed on the same tissues to facilitate an integrated proteogenomic analysis and determine the impact of genomic alterations on protein expression, signaling pathways, and post-translational modifications. To ensure robust downstream analyses, tumor neoplastic cellularity was assessed via …