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Commit 037eddb7 authored by Gervaise Henry's avatar Gervaise Henry :cowboy:
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Update research+people & move html out of md & update blackburn theme

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baseurl = "https://www.StrandLab.net/" baseurl = "https://www.StrandLab.net/"
title = "Strand Lab" title = "Strand Lab"
author = "Gervaise H. Henry" author = "Gervaise H. Henry"
theme = "blackburn"
# Shown in the side menu # Shown in the side menu
copyright = "© 2019. All rights reserved." copyright = "© 2019. All rights reserved."
canonifyurls = true canonifyurls = true
...@@ -28,45 +29,41 @@ paginate = 10 ...@@ -28,45 +29,41 @@ paginate = 10
custom_css = [""] custom_css = [""]
custom_js = [""] custom_js = [""]
[params.piwikAnalytics]
siteid = 2
piwikroot = ""
[menu] [menu]
# Shown in the side menu. # Shown in the side menu.
[[menu.main]] [[menu.main]]
name = "Research" name = "Research"
pre = "<i class='fa fa-home fa-fw'></i>" pre = "<i class='fas fa-home fa-fw'></i>"
weight = 1 weight = 1
identifier = "research" identifier = "research"
url = "/research" url = "/research"
[[menu.main]] [[menu.main]]
name = "People" name = "People"
pre = "<i class='fa fa-user fa-fw'></i>" pre = "<i class='fas fa-user fa-fw'></i>"
weight = 2 weight = 2
identifier = "people" identifier = "people"
url = "/people/" url = "/people/"
[[menu.main]] [[menu.main]]
name = "Publications" name = "Publications"
pre = "<i class='fa fa-book fa-fw'></i>" pre = "<i class='fas fa-book fa-fw'></i>"
weight = 3 weight = 3
identifier = "publications" identifier = "publications"
url = "/publications/" url = "/publications/"
[[menu.main]] [[menu.main]]
name = "Biorepository" name = "Biorepository"
pre = "<i class='fa fa-stethoscope fa-fw'></i>" pre = "<i class='fas fa-stethoscope fa-fw'></i>"
weight = 4 weight = 4
identifier = "repository" identifier = "repository"
url = "/repository/" url = "/repository/"
[[menu.main]] [[menu.main]]
name = "Single-Cell Data" name = "Single-Cell Data"
pre = "<i class='fa fa-bar-chart fa-fw'></i>" pre = "<i class='fas fa-chart-bar fa-fw'></i>"
weight = 5 weight = 5
identifier = "data" identifier = "data"
url = "/data" url = "/data"
[[menu.main]] [[menu.main]]
name = "Contact" name = "Contact"
pre = "<i class='fa fa-phone fa-fw'></i>" pre = "<i class='fas fa-phone fa-fw'></i>"
weight = 6 weight = 6
url = "/contact" url = "/contact"
......
...@@ -2,75 +2,6 @@ ...@@ -2,75 +2,6 @@
title: "KEEP IN TOUCH WITH US" title: "KEEP IN TOUCH WITH US"
date: 2019-05-19T13:49:34-05:00 date: 2019-05-19T13:49:34-05:00
draft: true draft: true
type: "custom"
layout: "contact"
--- ---
<style>
.map {
position: relative;
padding-bottom: 50%;
height: 0;
overflow: hidden;
}
.map iframe {
position: absolute;
top: 0;
left: 0;
width: 100% !important;
height: 100% !important;
}
@media (min-width: 1000px) {
.column {
float: left;
}
.left {
width: 10%;
}
.right {
width: 90%;
}
.row:after {
content: "";
display: table;
clear: both;
}
}
</style>
<p style='text-align: center;'>
Questions about our research or need a tip on one of our protocols? Interested in collaborations? Email us, mention any person, project, or activity of interest,and we will get back to you soon!
</p>
<div class="map">
<iframe src="https://www.google.com/maps/embed?pb=!1m14!1m12!1m3!1d5666.067598000117!2d-96.84034317995817!3d32.81593873821668!2m3!1f0!2f0!3f0!3m2!1i1024!2i768!4f13.1!5e0!3m2!1sen!2sus!4v1558292028882!5m2!1sen!2sus" frameborder="0" style="border:0" allowfullscreen></iframe>
</div>
<div class="row">
<div class="column left">
<i class="fa fa-map-marker fa-2x"></i><br>
</div>
<div class="column right">
UT Southwestern Medical Center,<br>
Department of Urology,<br>
5323 Harry Hines Blvd,<br>
Mail Code: 9110,<br>
Dallas, TX 75390-9110<br>
</div>
</div>
___
<div class="row">
<div class="column left">
<i class="fa fa-envelope-open fa-2x"></i><br>
</div>
<div class="column right">
[douglas.strand@utsouthwestern.edu](mailto:douglas.strand@utsouthwestern.edu)
</div>
</div>
___
<div class="row">
<div class="column left">
<i class="fa fa-phone fa-2x"></i><br>
</div>
<div class="column right">
214-648-6096
</div>
</div>
___
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...@@ -5,119 +5,3 @@ draft: true ...@@ -5,119 +5,3 @@ draft: true
type: "custom" type: "custom"
layout: "data" layout: "data"
--- ---
<style>
.content{
margin: 0;
max-width: none;
}
.select {
float: top;
z-index: 1;
top: 0px;
background: #191818;
overflow-x: hidden;
padding: 8px 10px;
}
.columnS {
float: left;
text-align: center;
width: 33.33%;
}
.columnF {
float: left;
text-align: center;
width: 33.33%;
}
.row:after {
content: "";
display: table;
clear: both;
}
img{
max-width: 100%;
height: auto;
}
@media (max-width: 1000px) {
.columnS {
text-align: right;
width: 100%;
}
.columnF {
width: 100%;
}
br {
display: none;
}
}
</style>
<body>
<div class = "select">
<div class = "columnS ui-widget">
<label for = "gene" style="font-family:sans-serif; font-size:18px;"><b>Gene:</b></label>
<br>
<input id = "gene">
</div>
<div class = "columnS">
<label for="lineage" style="font-size:18px;"><b>Select a cell lineage to display:</b></label>
<br>
<select name="lineage" id="lineage">
<option selected="selected" value="all">All Cells</option>
<option value="epi">Epithelial Cells Only</option>
<option value="st">Stromal Cells Only</option>
</select>
</div>
<div class = "columnS">
<label for="populations" style="font-size:18px;"><b>Select a group of cell populations:</b></label>
<br>
<select name="populations" id="populations">
<option>Lineage</option>
<option>Patient</option>
<option selected="selected" value="Populations"> Cell Populations</option>
<option value="Zone">Prostatic Zone</option>
</select>
</div>
<br>
<button type="submit" id="analysis" class="btn btn-primary">Run Analysis</button>
<hr>
<div>
<span style="font-size:16px; font-weight:bold; " >Experimental details:</span>
<br>
<span style="font-size:16px;">Single Cell RNA-Sequencing was conducted on 32,194 cells from peripheral zone and transition zone from the prostate of three 18-38 year old organ donors using the 10x Genomics platform. The cells were clustered and identified by correlation of their transcriptomes to known cell types. Gene expression can be compared by population identity, cell lineage, patient, or dissected prostatic zone.</span>
</div>
</div>
<div align = "center">
<h1 id="label.gene">NO GENE SELECTED</h1>
<h2 id="label.lineage"></h2>
<h3 id="label.populations"></h3>
<div class = "columnF">
<h4 id="label.ClusterVis"></h3>
<div class = "img">
<img id="img.ClusterVis" src=""/>
</div>
<br>
</div>
<div class = "columnF">
<h4 id="label.Feature"></h3>
<div class = "img">
<img id="img.Feature" src=""/>
</div>
<br>
</div>
<div class = "columnF">
<h4 id="label.ViolinBox"></h3>
<div class = "img">
<img id="img.ViolinBox" src=""/>
</div>
<br>
</div>
</div>
<hr>
<div align = "left">
<div><span style="font-size:18px; font-weight:bold; " >Publication found at:</span></div>
<div><span style="font-size:16px;" > <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=30566875">Cell Reports</a></span></div>
<div><span style="font-size:18px; font-weight:bold;" >Raw data found at:</span></div>
<div><span style="font-size:16px;" > <a href="https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE117403">GEO: GSE117403</a></span></div>
<div><span style="font-size:16px;" ><a href="https://doi.org/10.25548/W-R8CM">GUDMAP: W-R8CM</a></span></div>
</div>
</body>
...@@ -12,4 +12,4 @@ current: true ...@@ -12,4 +12,4 @@ current: true
--- ---
<!--Weight: 1=PI 2=Faculty 3=Instructors 4=PostDocs 5=Techs 6=GradStudents 10=Other 15=Interns--> <!--Weight: 1=PI 2=Faculty 3=Instructors 4=PostDocs 5=Techs 6=GradStudents 10=Other 15=Interns-->
Gervaise obtained his master's degree at American University in 2015. He joined Dr. Strand’s lab in 2015. Gervaise obtained his master's degree at American University in 2015. He joined Dr. Strand's lab in 2015. His previous experience involved the utilization of a diverse set of molecular techniques to investigate cancer biology. He also has a strong background in early-stage drug discovery, including the use of lab robotics. After a very successful fellowship with UT Southwestern Bioinformatics Department's Bioinformatics Core Facility (BICF), he transitioned to a more computational role in the lab. He is responsible for the analysis of sequencing, in particular single-cell RNA-sequencing analysis. He also builds pipelines for automated analysis, and tools for easy data exploration.
\ No newline at end of file \ No newline at end of file
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...@@ -2,9 +2,9 @@ ...@@ -2,9 +2,9 @@
title: "Joseph_d" title: "Joseph_d"
date: 2019-05-18T21:33:56-05:00 date: 2019-05-18T21:33:56-05:00
draft: true draft: true
name: "Diya B. Joseph" name: "Diya Binoy Joseph"
degree: "Ph.D." degree: "Ph.D."
pic: "joseph_d.jpeg" pic: "joseph_d.jpg"
tit: "Postdoctoral Researcher" tit: "Postdoctoral Researcher"
orcid: "0000-0002-0587-9558" orcid: "0000-0002-0587-9558"
weight: "4" weight: "4"
...@@ -12,4 +12,4 @@ current: true ...@@ -12,4 +12,4 @@ current: true
--- ---
<!--Weight: 1=PI 2=Faculty 3=Instructors 4=PostDocs 5=Techs 6=GradStudents 10=Other 15=Interns--> <!--Weight: 1=PI 2=Faculty 3=Instructors 4=PostDocs 5=Techs 6=GradStudents 10=Other 15=Interns-->
Diya obtained her PhD at the University of Wisconsin: Madison in the Vezina Lab. She joined the Dr. Strand's Lab in 2019. Diya joined the Strand lab in January 2019 as a postdoctoral researcher. Prior to this, she received her Bachelor's degree in Biotechnology from the National Institute of Technology, Calicut in India in 2013 and a Ph.D in Cellular and Molecular Biology in December 2018 from the University of Wisconsin-Madison. During her doctoral studies in Dr. Chad Vezina's lab, Diya studied the development of the lower urinary tract with special emphasis on the role of DNA methylating enzymes during prostate development. During her doctoral studies, Diya was part of a collaborative project with Dr. Strand to produce the first cellular anatomy of the normal human prostate at single cell resolution. This collaboration led to her current position as a postdoctoral researcher in the Strand lab where she studies Benign Prostatic Hyperplasia (BPH) and the role of novel club and hillock urethral cell types in BPH growth.
\ No newline at end of file \ No newline at end of file
...@@ -12,4 +12,4 @@ current: true ...@@ -12,4 +12,4 @@ current: true
--- ---
<!--Weight: 1=PI 2=Faculty 3=Instructors 4=PostDocs 5=Techs 6=GradStudents 10=Other 15=Interns--> <!--Weight: 1=PI 2=Faculty 3=Instructors 4=PostDocs 5=Techs 6=GradStudents 10=Other 15=Interns-->
Doug obtained his Ph.D. with David Rowley at Baylor College of Medicine in the department of Molecular and Cellular Biology. He did a postdoctoral fellowship at Vanderbilt University under Simon Hayward. He joined the faculty of UTSW in 2014. Doug obtained his Ph.D. with David Rowley at Baylor College of Medicine in the department of Molecular and Cellular Biology. He did a postdoctoral fellowship at Vanderbilt University under Simon Hayward. He joined the faculty of UTSW in 2014 and works closely with the clinicians in the Urology department to characterize the cellular pathogenesis of diseases of the human lower urinary tract.
\ No newline at end of file \ No newline at end of file
content/research.images/prostate.jpg

33.7 KiB

...@@ -2,85 +2,6 @@ ...@@ -2,85 +2,6 @@
title: "Research" title: "Research"
date: 2019-05-19T01:57:56-05:00 date: 2019-05-19T01:57:56-05:00
draft: true draft: true
type: "custom"
layout: "research"
--- ---
<style>
div.section:after {
content: "";
display: table;
clear: both;
}
div.fig {
max-width: 500px;
padding: 1px;
border: 1px solid black;
margin: 1px 10px 1px 1px;
}
div.fig img {
width: 500px;
max-width: 100%;
height: auto;
padding: 1px;
}
div.lab {
text-align: justify;
padding-left: 10px;
padding-right: 10px;
}
@media (min-width: 1000px) {
div.fig {
float: left;
}
br {
display: none;
}
}
</style>
<div class="section">
<H1 align="center">BENIGN PROSTATIC HYPERPLASIA</H1>
<div class="fig">
<img src="/research.images/disease.jpg" alt="disease"/>
<p class="br"></p>
</div>
<p style="text-align:justify; font-size:18px;">
The goal of the Strand laboratory is to understand the cellular and molecular biology of benign prostatic hyperplasia (BPH). The prostate is a walnut-sized organ wrapped around the bladder neck. A majority of men over 70 years old have BPH, which can cause lower urinary tract symptoms and voiding dysfunction. First line treatment for men with moderately symptomatic BPH is typically an alpha blocker to relax smooth muscle tone. Once the prostate enlarges over 40cc, 5 alpha reductase inhibitors are administered, which reduce prostate volume by ~20% through apoptosis of luminal epithelia. These drugs are mostly tolerable and reduce symptomatic progression by 33% individually. Although the introduction of these drugs decreased surgical intervention, hundreds of thousands of surgeries are performed each year in the US to reduce prostate volume in elderly men. A better understanding of the biology of BPH is needed to develop drugs that actually target the causes of prostatic enlargement and reduce surgical intervention.
</p>
</div>
<div class="section">
<H1 align="center">PATHOLOGICAL HETEROGENEITY AND PERSONALIZED MEDICINE FOR BPH</H1>
<div class="fig">
<img src="/research.images/pheno.jpg" alt="phenotypes" class="img"/>
<div class="lab">
<p>BPH is morphologically diverse. Patients can present with purely glandular hyperplasia, purely stromal hyperplasia, or a mixture of both phenotypes as shown in these images of fresh tissue and a corresponding whole mount H&E.</p>
</div>
<p class="br"></p>
</div>
<p style="text-align:justify; font-size:16px;">
BPH is morphologically diverse. Patients can present with purely glandular hyperplasia, purely stromal hyperplasia, or a mixture of both phenotypes as shown in these images of fresh tissue and a corresponding whole mount H&E.
</p>
<p style="text-align:justify; font-size:18px;">
One of the factors that likely causes a variable response to medical therapy is phenotypic heterogeneity. Alpha blockers target normal smooth muscle and 5ARIs target normal luminal epithelia. These drugs were not developed to target pathways altered in diseased cells because cell type-specific alterations in BPH have not yet been characterized. Furthermore, each patient can display a highly variable proportion of these cell types in BPH and they are most certainly no longer normal. No clinical trial has ever taken into account the role of cellular composition in treatment response. Our goal is to characterize the cellular composition of BPH, establish clinically useful imaging modalities or biomarkers to diagnose the BPH phenotype, and develop targeted therapies based on cellular and molecular data.
</p>
</div>
<div class="section">
<H1 align="center">CELLULAR ANATOMY OF THE HUMAN PROSTATE</H1>
<div class="fig">
<img src="/research.images/disection.jpg" alt="disection" class="img"/>
<div class="lab">
<p>The human prostate sits at the base of the bladder, which releases urine through the prostatic urethra. Ureters connect to the kidneys, vas deferens connect to the testicles. Sperm from the testicles, and secretory fluids from the seminal vesicles and prostate are forced through into the prostatic urethra during ejaculation. The human prostate is divided into 4 major ‘zones’: the transition zone (TZ), which is an area than encircles the prostatic urethra from the base at the bladder neck to the apex at the start of the penis; the central zone (CZ) encircles the ejaculatory ducts from the seminal vesicles; the peripheral zone (PZ) encompasses the posterior prostate surrounding the TZ and CZ; and the anterior fibromuscular stroma (AFS).</p>
</div>
<p class="br"></p>
</div>
<p style="text-align:justify; font-size:18px;">
The human prostate sits at the base of the bladder, which releases urine through the prostatic urethra. Ureters connect to the kidneys, vas deferens connect to the testicles. Sperm from the testicles, and secretory fluids from the seminal vesicles and prostate are forced through into the prostatic urethra during ejaculation. The human prostate is divided into 4 major ‘zones’: the transition zone (TZ), which is an area than encircles the prostatic urethra from the base at the bladder neck to the apex at the start of the penis; the central zone (CZ) encircles the ejaculatory ducts from the seminal vesicles; the peripheral zone (PZ) encompasses the posterior prostate surrounding the TZ and CZ; and the anterior fibromuscular stroma (AFS).
</p>
<p style="text-align:justify; font-size:18px;">
The first step towards personalized therapy for BPH phenotypes is to understand the cellular anatomy of the normal prostate. The prostate is mainly composed of epithelial and stromal cell types. Historically, the definition of prostate epithelial cell type has been based on 1) the relative position of cells within glandular acini, 2) cellular shape, and 3) the differential expression of genes and cell surface antigens. Using these criteria, prostate glands are reportedly composed of basal and luminal epithelia with rare neuroendocrine cells. Basal epithelia express cytokeratins 5 / 14 as well as the transcription factor p63. Luminal epithelia express cytokeratins 8 / 18 as well as androgen receptor. A putative intermediate cell ‘state’ between luminal and basal lineages has been defined on the basis of shared expression of luminal and basal cytokeratins. Neuroendocrine epithelia are defined by expression of markers such as chromogranin A. The stroma is even more poorly defined as generic smooth muscle and fibroblast cell types. Our laboratory is using single cell sequencing and flow cytometry to define the cellular composition of the normal prostate procured from young organ donors through a partnership with the Southwest Transplant Alliance. These data will establish a baseline against which various diseased phenotypes can be compared. We currently have a biorepository of normal and diseased human prostate containing paraffin blocks, OCT blocks, flash frozen tissue, and cryopreserved single cells available upon request (see Resources page). You can also search our single cell sequencing dataset with our ProstateMapper tool to see where your gene of interest is expressed in the normal prostate.
</p>
</div>
\ No newline at end of file
{{ partial "header.html" . }}
<div class="header">
<h1>{{ .Title }}</h1>
<h2>{{ .Description }}</h2>
</div>
<div class="content">
<p style="text-align: center">
Questions about our research or need a tip on one of our protocols?
Interested in collaborations? Email us, mention any person, project, or
activity of interest,and we will get back to you soon!
</p>
<hr>
<div style="text-align: center">
<iframe
src="https://www.google.com/maps/embed?pb=!1m18!1m12!1m3!1d3353.0540362781526!2d-96.84412528424524!3d32.81733318923467!2m3!1f0!2f0!3f0!3m2!1i1024!2i768!4f13.1!3m3!1m2!1s0x864e9c04b088e599%3A0x2e63ea34f8b2150b!2sUT%20Southwestern%20Medical%20Center!5e0!3m2!1sen!2sus!4v1576207208811!5m2!1sen!2sus"
width="600" height="450" frameborder="0" style="border:0"
allowfullscreen=""></iframe>
</div>
<hr>
<div style="text-align: center">
<i class="fa fa-map-marker"></i>
UT Southwestern Medical Center,<br>
Department of Urology,<br>
5323 Harry Hines Blvd,<br>
Mail Code: 9110,<br>
Dallas, TX 75390-9110<br>
</div>
<hr>
<div style="text-align: center">
<i class="fa fa-envelope-open"></i>
<a href="mailto: douglas.strand@utsouthwestern.edu">douglas.strand@utsouthwestern.edu</a>
</div>
<hr>
<div style="text-align: center">
<i class="fa fa-phone"></i>
214-648-6096
</div>
<hr>
{{ partial "footer.html" . }}
\ No newline at end of file
{{ partial "header.html" . }} {{ partial "header.html" . }}
<div class="header"> <div class="header">
<h1>{{ .Title }}</h1> <h1>{{ .Title }}</h1>
<h2>{{ .Description }}</h2> <h2>{{ .Description }}</h2>
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<div class="content"> <div class="content">
{{ .Content }} {{ .Content }}
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{{ partial "footer.html" . }} <style>
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}
.select {
float: top;
z-index: 1;
top: 0px;
background: #191818;
overflow-x: hidden;
padding: 8px 10px;
}
.columnS {
float: left;
text-align: center;
width: 33.33%;
}
.columnF {
float: left;
text-align: center;
width: 33.33%;
}
.row:after {
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display: table;
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img{
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@media (max-width: 1000px) {
.columnS {
text-align: right;
width: 100%;
}
.columnF {
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}
br {
display: none;
}
}
</style>
<body>
<div class="select">
<div class="columnS ui-widget">
<label for="gene" style="font-family:sans-serif; font-size:18px;"><b>Gene:</b></label>
<br>
<input id="gene" size="19">
</div>
<div class="columnS">
<label for="lineage" style="font-size:18px;"><b>Select a cell lineage to
display:</b></label>
<br>
<select name="lineage" id="lineage">
<option selected="selected" value="all">All Cells</option>
<option value="epi">Epithelial Cells Only</option>
<option value="st">Stromal Cells Only</option>
</select>
</div>
<div class="columnS">
<label for="populations" style="font-size:18px;"><b>Select a group of cell
populations:</b></label>
<br>
<select name="populations" id="populations">
<option>Lineage</option>
<option>Patient</option>
<option selected="selected" value="Populations"> Cell Populations</option>
<option value="Zone">Prostatic Zone</option>
</select>
</div>
<br>
<button type="submit" id="analysis" class="btn btn-primary">Run Analysis</button>
<hr>
<div>
<span style="font-size:16px; font-weight:bold;">Experimental details:</span>
<br>
<span style="font-size:16px;">Single Cell RNA-Sequencing was conducted on
32,194 cells from peripheral zone and transition zone from the prostate
of three 18-38 year old organ donors using the 10x Genomics platform.
The cells were clustered and identified by correlation of their
transcriptomes to known cell types. Gene expression can be compared by
population identity, cell lineage, patient, or dissected prostatic zone.</span>
</div>
</div>
<div align="center">
<h1 id="label.gene">NO GENE SELECTED</h1>
<h2 id="label.lineage"></h2>
<h3 id="label.populations"></h3>
<div class="columnF">
<h4 id="label.ClusterVis"></h3>
<div class="img">
<img id="img.ClusterVis" src="" />
</div>
<br>
</div>
<div class="columnF">
<h4 id="label.Feature"></h3>
<div class="img">
<img id="img.Feature" src="" />
</div>
<br>
</div>
<div class="columnF">
<h4 id="label.ViolinBox"></h3>
<div class="img">
<img id="img.ViolinBox" src="" />
</div>
<br>
</div>
</div>
<hr>
<div align="left">
<div><span style="font-size:18px; font-weight:bold;">Publication found at:</span></div>
<div><span style="font-size:16px;"> <a
href="https://www.ncbi.nlm.nih.gov/pubmed/?term=30566875"
target="_blank">Cell Reports</a></span></div>
<div><span style="font-size:18px; font-weight:bold;">Raw data found at:</span></div>
<div><span style="font-size:16px;"> <a
href="https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE117403"
target="_blank">GEO:
GSE117403</a></span></div>
<div><span style="font-size:16px;"><a
href="https://doi.org/10.25548/W-R8CM" target="_blank">GUDMAP: W-R8CM</a></span></div>
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<H1 align="center">Overview</H1>
<p style="text-align:justify; font-size:18px">
The main goals of the Strand lab are to create accurate cellular
atlases of the human and mouse lower
urinary tract, characterize the molecular and cellular alterations
in human lower urinary tract disease, and
build appropriate models of the human disease in novel mouse models.
</p>
</div>
<div class="section">
<H1 align="center">Benign Prostatic Hyperplasia</H1>
<div class="fig" style="max-width:250px">
<img src="/research.images/prostate.jpg" alt="prostate" class="img"
/>
<div class="lab">
<p>Cross-section of a prostate gland, showing the transition
zone (TZ) and the peripheral zone (PZ)</p>
</div>
<p class="br"></p>
</div>
<p style="text-align:justify; font-size:18px">
A goal of the Strand laboratory is to understand the cellular and
molecular biology of lower urinary tract
symptoms (LUTS) due to benign prostatic hyperplasia (BPH) or bladder
dysfunction. BPH/LUTS is present in the
vast majority of men over 70 years old resulting in medical
treatment or surgical intervention.
</p>
<p style="text-align:justify; font-size:18px">
We focus on translational questions related to progression of
BPH/LUTS in order to develop new targets for
therapeutic intervention. In particular, we are interested in
characterizing the cellular composition of
particular phenotypes that are resistant to current therapies. We
use a combination of single cell RNA
sequencing, flow cytometry and immunohistochemistry on normal and
diseased human specimens to build a
cellular atlas of prostate and bladder disease.
</p>
</div>
<div class="section">
<H1 align="center">Pathological Heterogeneity in BPH</H1>
<div class="fig" style="max-width:500px">
<img src="/research.images/pheno.jpg" alt="phenotypes" class="img"
/>
<div class="lab">
<p>Phenotypic diversity in BPH. Left: glandular enlargement.
Middle: Stromal enlargement. Right: Mixed
type.</p>
</div>
</div>
<p style="text-align:justify; font-size:18px">
We believe that the basis for heterogeneous clinical responses in
BPH is pathologic diversity. There are a
number of phenotypes evident across and even within patients. In one
area, a patient can display a stromal
tumor while the other area display an epithelial nodule.
</p>
<p style="text-align:justify; font-size:18px">
Our goal is to provide a rational basis for therapeutically treating
these individual phenotypes by
dissecting them macroscopically and then comparing their
cell-specific molecular profiles to reduce the
noise of cellular heterogeneity and inflammation. Our first goal is
to identify a cell or cells of origin
for the varying phenotypes by phenotyping the tissues with single
cell RNA sequencing. This includes a
comprehensive evaluation of the immune and inflammatory infiltrate
as well as fluctuations in epithelial and
stromal subpopulations.
</p>
<p style="text-align:justify; font-size:18px">
We are subsequently isolating the cell types of interest and
performing molecular profiling. Based on these
targets, we will use our mouse and cell culture models to
experimentally test our hypotheses.
</p>
</div>
<div class="section">
<H1 align="center">Clinical Heterogeneity in BPH</H1>
<p style="text-align:justify; font-size:18px">
It is clear from clinical trials of medications for BPH that
personalized therapies will be needed due to
the highly variable responses. Typically, patients complaining of
lower urinary tract symptoms are placed on
an alpha-adrenergic receptor blocker as a first line therapy due to
its fast-acting relief of symptoms.
These drugs relieve smooth muscle tone and are most effective in
patients with early stage disease
displaying a high smooth muscle to epithelial tissue composition.
However, as the prostate enlarges,
epithelial nodules predominate the tissue decreasing the likelihood
of alpha-blocker efficacy.
</p>
<p style="text-align:justify; font-size:18px">
The second-line therapy for BPH is a 5 alpha reductase inhibitor
(5ARI), which induces epithelial apoptosis
by decreasing the levels of intra-prostatic dihyrotestosterone
(DHT). This therapy is effective at reducing
prostate size by 25 percent in most patients.
</p>
<p style="text-align:justify; font-size:18px">
Importantly, either therapy only reduces symptomatic progression by
34 percent, suggesting
androgen-independent mechanisms of prostate growth and symptoms need
to be targeted. Responses to current
drugs are further reduced in patients with obesity, diabetes, and
dyslipidemia.
</p>
<p style="text-align:justify; font-size:18px">
These data suggest that there are further measures that are
necessary for every patient, and completely
novel measures necessary for individual patients. Our goal is to
characterize the cellular composition of
particular phenotypes, and more deeply understand the molecular
changes driving these phenotypes. We use a
combination of single cell RNA sequencing, flow cytometry, and
immunohistochemistry on specimens from young
organ donors and older men with prostatic enlargement.
</p>
</div>
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