Latest Research - Thank EWE!

LAM Update 2016

Our team has created LAM-like cells which we share with other researchers around the world. Some cells have even been accepted at Harvard! We miss them but know this is a great opportunity. Other cells are living the high life in Montreal with another collaborator, Dr. Kristof. 

When we injected the human LAM-like cells into the lungs of female mice, 2 months later we discovered LAM nodules growing in the mouse LUNGS! This is a significant breakthrough. The lab can now compare the LAM nodules in mouse lungs with those in real life LAM patients and conduct experiments to determine what happens to the nodules in 6 months. This may provide a model patient for testing new LAM drugs. The lab is also testing to see if this happens in male mice which leads us to the conclusion of why LAM only happens in women! 

About those LAM drugs… The lab has developed three types of tests for new LAM drugs: 1) the ability to kill LAM cells specifically; 2) the ability to turn off the destructive proteins called MMPs that LAM cells produce which make the holes in the lungs of LAM patients; and 3) the ability to stop LAM cells from roaming around the body and causing havoc. Rapamycin and a few select drugs are being tested right NOW before going prime time with testing hundreds of drugs this summer!

Sheep happens 🐏 and this research is only happening because of YOU. MANY THANKS to each and every one of EWE!  


LAM Update 2014

Frontiers in Cell and Developmental Biology

Accelerating Discovery LAM Disease
Research Project: “Be Part of a Cure!”

Project Outline:

Lymphangioleiomyomatosis (LAM) disease is a rare pulmonary disease that primarily
attacks women, most often in the prime of their lives, between the ages of 25 to 40.
Often sufferers look completely healthy, but their lungs are developing cysts and are
slowly being destroyed. There is no cure. Though there are drugs that can slow disease
progression, the only treatment is complete lung transplant. This is typically required
within three years of diagnosis or the disease is fatal. The rarity of the
disease makes it challenging to diagnose, and even more difficult to study
and secure funding for research. Led by Dr. Bill Stanford at Ottawa Hospital
Research Institute, through a unique collaboration, McEwen Centre
scientists will drive research in four separate laboratories in search of
a cause and a cure for LAM disease.

World-class Team of Scientists:

Bill Stanford, Molly S. Shoichet, Freda Miller, Tom Waddell and Peter Zandstra.

Research Overview:

Recent thinking about LAM disease is that it is a form of cancer – but one that does not
behave like any other cancer. Basic research has demonstrated that the TSC2 gene is
usually mutated in LAM. The TSC2 gene is important because it regulates cell growth
and communication between cells by activating signalling pathways between cells. What
is not clear is: what other genes mutate?; do they mutate before or after TSC2; what is
the cell of origin; and what is “normal” behaviour of a cancer cell and what is abnormal?
If we can show that LAM cells are cancer like neural crest cells then we develop targeted
therapies based on that information.

Objectives:

The biggest roadblock to advancing LAM research is that, thus far, scientists have
been unable to keep the cells alive in a dish long enough to study the effects of various
treatment regimens. Shortly after the cells are removed from a patient’s lungs, they
either die or are overgrown by normal cells; making extended observation impossible.
The goal for this Accelerating Discovery Initiative is to generate a viable cell culture
model of LAM. Once this is achieved, drug screening can commence.

Four Projects:

1) Develop a method to grow LAM cells, isolated from patients and stem cells,
in culture (Shoichet and Stanford).

By combining chemical engineering expertise (Shoichet), stem cell biology and LAM
expertise (Stanford), we will analyze natural and artificial chemicals that will mimic the
lung environment and coax LAM cells to grow in culture. This will allow us to perform
an array of experiments to understand LAM and to perform drug screens.

2) Derivation of LAM models via tumor derived iPSC generation and
differentiation (Stanford).

Because we do not yet know how to persuade LAM cells to grow in culture, we will make
stem cells called induced pluripotent stem cells (iPSCs) from LAM and then differentiate
the iPSCs into LAM cells to perform experiments in cell culture, animal models and
drug screens.

3) Derivation of LAM models via zinc finger nuclease mediated knockout
of TSC2 in hESCs and subsequent differentiation (Stanford).

To understand how important TSC2 gene mutations are for LAM initiation and progression
we will delete the TSC2 gene in human embryonic stem cells and then differentiate
these stem cells into LAM cells to perform experiments in cell culture, animal models
and drug screens. If there is a difference, then we know that additional mutations
are important in LAM and we will track those mutations down using DNA sequencing
technologies.

4) Derivation of LAM models via zinc finger nuclease mediated knockout
of TSC2 in SKPs, a neural crest progenitor (Stanford, Miller).

In this project, we will side step making stem cells by using stem like cells found in the
skin. We will make the TSC2 mutation in SKPs for use in cell culture, animal model
experiments and drug screens. This strategy will directly test conventional wisdom that
suggests that LAM is a disease of the neural crest stem cell.

Drs. Miller, Waddell, and Zandstra will provide expert consultation, training, and tissue
samples for the projects outlined above.

Research Progress:

Through a multi-pronged research approach over the last 8 months, the project teams
have made progress in developing the technical program for screening the mutations.
The screening is critical for re-creating the disease in a dish for drug screening to be viable.
This success is incremental and essential in the progress of the project to achieve the overall
goal and the progress to date has informed the direction of the research going forward.

There is never a direct path to discoveries and incremental advancements in learning
what isn’t going to work is helpful in reaching the conclusion. Dr. Stanford and his team
have made significant advancement towards narrowing down the path to achieve the
outcome in what is a short period of time.

Fundraising Goal:

$300,000/year for 3 years.


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