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impact.html
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---
layout: default
redirect_from: "/impact.shtml"
---
<h1>
Impact on human health
</h1>
<p>
Our CellProfiler software has yielded discoveries in several
translational projects, some of which may ultimately have a direct
impact on the treatment of disease. For example, CellProfiler has
been used to identify several small molecules that are effective in
treating particular diseases in mouse models. In some cases,
discoveries made using CellProfiler have even led to planning
clinical trials in humans, which could directly improve patient
outcomes. Here we highlight instances that have come to our
attention. [See also: <a href=
"http://cellprofiler.org/citations.html">citations]</a>
</p>
<h2 style="font-style:italic;">
Ebola Virus
</h2>
<a href="https://www.flickr.com/photos/niaid/16441626349/"><img alt=
"CellProfiler Ebola disease image" src="http://d1zymp9ayga15t.cloudfront.net/images/ebola.png" style=
"float:right; padding-left:10px;" width="160" /></a>
<p>
The 2014 outbreak of the Ebola virus in West Africa has claimed the
lives of over 8,600 people worldwide; the disease currently has no
approved cure or vaccine. CellProfiler was used to identify
therapeutic targets within host human macrophages capable of halting
infection by inhibiting viral uptake via cell surface proteins and
endosomal trafficking. The <a href=
"http://www.txbiomed.org/departments/virology/virology-staff-bio/?u=185">
Davey</a> lab at the Texas Biomedical Research Institute found that
Tetrandrine, an isolate from Chinese and Japanese herbs but now
produced synthetically, was especially potent in blocking two-pore
channels found in endosomes, and preliminary studies showed high
therapeutic efficacy in mice without obvious side effects.
</p>
<p>
<span style="font-style:italic;">For more details</span>: Sakurai Y
et al. (2015) Two-pore channels control Ebola virus host cell entry
and are drug targets for disease treatment. Science, 347(6225)
995-998 (<a href=
"http://www.sciencemag.orghttp://d1zymp9ayga15t.cloudfront.net/content/347/6225/995.full">paper</a>,
<a href=
"http://www.txbiomed.org/news-press/detail/news/2015/02/26/research-shows-asian-herb-holds-promise-as-treatment-for-ebola-virus-disease">
press release</a>)
</p>
<br />
<h2 style="font-style:italic;">
Tuberculosis
</h2>
<img alt="Mycobacterium tuberculosis (Mtb) CellProfiler image-analysis"
src="http://d1zymp9ayga15t.cloudfront.net/images/Tuberculosis.png" style="float:right; padding-left:10px;"
width="160" />
<p>
Tuberculosis (TB) is a disease of global concern due in part to
increasingly antibiotic-resistant bacteria. CellProfiler was used in
a high-throughput screen of bioactive small molecules to identify
those that inhibited growth of Mycobacterium tuberculosis (Mtb)
within host cells by targeting host functions and pathways. Notably,
among the identified effective compounds were fluoxetine (commonly
known as Prozac) and gefitinib, used clinically for treating
depression and cancer, respectively. Gefitinib was subsequently
demonstrated to reduce Mtb growth in the lungs of infected mice. In
addition to identifying new pathways likely to be relevant for TB
pathogenesis, this work demonstrated that targeting the host may be a
viable adjunctive approach for treating TB.
</p>
<p>
<span style="font-style:italic;">For more details</span>: Stanley SA
et al. (2014). A chemical screen to identify host-targeting small
molecules that restrict intracellular Mycobacterium tuberculosis
growth. PLoS Pathogens, 10(2):e1003946 (<a href=
"http://dx.doi.org/10.1371/journal.ppat.1003946">paper</a>)
</p>
<br />
<h2 style="font-style:italic;">
Leukemia (AMKL)
</h2>
<img alt="CellProfiler Leukemia human megakaryocytes image analysis"
src="http://d1zymp9ayga15t.cloudfront.net/images/Polyploidy.png" style="float:right; padding-left:10px;"
width="160" />
<p>
CellProfiler helped to identify novel compounds that may lead to
potential treatments for a form of leukemia involving human
megakaryocytes (AMKL). Most cancer treatments work by targeting
cancer cells for death as compared to normal cells. By contrast, the
goal here was to search for drugs that can induce polyploidy, which
restrains the cancerous cells’ uncontrolled growth by causing them to
differentiate into a terminal state. Over 200 polyploidization
regulators were identified from a 10,000 compound screen. One hit in
particular, dimethylfasudil, a broad kinase inhibitor of Aurora
kinase A, also succeeded in inducing polyploidy in an AMKL mouse
model. The team turned its attention to the Aurora-A inhibitor
Alisertib which is already under clinical investigation for a variety
of tumors.
</p>
<p>
<span style="font-style:italic;">For more details</span>: Wen Q et
al. (2012). Identification of regulators of polyploidization presents
therapeutic targets for treatment of AMKL. Cell, 150(3):575-89
(<a href="http://dx.doi.org/10.1016/j.cell.2012.06.032">paper</a>,
<a href="http://www.broadinstitute.org/news/4289">press release</a>).
</p>
<br />
<h2 style="font-style:italic;">
Leukemia Stem Cells
</h2>
<img alt="CellProfiler Leukemia Leukemic stem cells image analysis"
src="http://d1zymp9ayga15t.cloudfront.net/images/Cobblestones.png" style="float:right; padding-left:10px;"
width="160" />
<p>
Cancer treatments directed towards leukemia can often fail due to the
survival of leukemic stem cells (LSCs) in the bone marrow. The
researchers screened 14,000 compounds in an unusually complex and
physiologically relevant in vitro co-culture system involving bone
marrow stromal cells and primary LSC-enriched cells. CellProfiler was
used together with the machine-learning capabilities of CellProfiler
Analyst to find compounds that inhibit LSC growth but do not affect
normal hematopoietic stem cells. One of the identified compounds was
lovastatin, a drug commonly used to treat high cholesterol. It
inhibited LSC growth in the co-culture system, as well as extended
the survival of mice with lovastatin-treated leukemic bone marrow
cells.
</p>
<p>
<span style="font-style:italic;">For more details</span>: Hartwell KA
et al. (2013) Nat Chem Biol, 9(12):840-8 (<a href=
"http://dx.doi.org/10.1038/nchembio.1367">paper</a>, <a href=
"http://www.broadinstitute.org/news/5323">press release</a>).
</p>
<br />
<h2 style="font-style:italic;">
Cerebral Cavernous Malformation (CCM)
</h2>
<a href=
"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356181/"><img alt="CellProfiler Cerebral Cavernous Malformation image analysis"
src="http://d1zymp9ayga15t.cloudfront.net/images/CCM.jpg" style="float:right; padding-left:10px;" width=
"160" /></a>
<p>
Researchers at the <a href=
"http://www.bioscience.utah.edu/faculty/molecular-biology-faculty/li/li.php">
University of Utah</a> used CellProfiler to identify image-based
phenotypes associated with a monogenic rare disease, the hereditary
stroke syndrome cerebral cavernous malformation (CCM). They then
identified known drugs that could reverse the phenotype and
demonstrated efficacy in a mouse model of CCM disease. This led to
the launching of <a href="http://www.recursionpharma.com/">Recursion
Pharmaceuticals</a>, which is pursuing a clinical trial for a
compound to treat CCM, which has no currently approved therapy. The
company will use a similar approach to identify compounds to target
other rare genetic diseases.
</p>
<p>
<span style="font-style:italic;">For more details</span>: Gibson CC
et al. (2015) Strategy for identifying repurposed drugs for the
treatment of cerebral cavernous malformation. Circulation,
131(3):289-99 (<a href=
"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356181/">paper</a>)
</p>
<br />