Harnessing our immune system to suppress Type 1 Diabetes
About the Researcher
Remi Creusot, PhD Assistant Professor
Columbia University Medical Center
6 Months - 1 year
What your donation will fund:
$3,500 raised:will cover the cost of optimizing, synthesizing and cloning 12 human genes (each providing a particular instruction when delivered into educator cells for expression).
$10,000 raised:will cover the above, plus the initial production of >100 ug RNA for each gene to be tested.
$15,000 raised:will cover the above, plus the cost of reagents to obtain educator cells and T cells from the blood of human donors.
$20,000 raised:will cover the above, plus the cost of reagents to assess T cell responses to signals provided.
- Gift Match
- Nob Li
- Kurt Wolf
- harlan pruden
- Katie Lagvilava
- Marck Gorszwick
- Dzuy-Thanh Luong
- Miyako Tomimasu
- Justine Chia
- robin skolnick
- Giulia Pertusati
- Kami Richardson
- Travis Richardson
- Remi Creusot, PhD
- Matt Luce
- Nicole Shapiro
- Jesse Khong
- Jesse Khong
- Nicole Shapiro
- Tom Wuyts
- Adrien Lanusse
- Matt Taylor
- Lily Khong
- Frank Farm
- garry fathman
- Remi Creusot
- Isadora Capozzi
- Tobi Schmidt
- Kurt Wolf
- Suparna Dutt
- Andy Tong
- Jeff deRhodes
- Jennifer Pfeifer
- Carol Grierson
- Megan Sykes
- Shahriar Yaghoubi
- randy pi
- san khong
- Jack Lin
- Daniel Byrd
- James Imper
- Mary Pat Gallagher
- Julian Finkelstein
Type 1 Diabetes (T1D) not only affects 1 in 300 children by the age of 18 in the US, but its incidence is on the rise worldwide, increasing 2-5% each year. The disease may also develop more slowly and manifest itself during adulthood. In the US alone, as many as 3 million people may have T1D, and more than 30,000 new cases are diagnosed each year, half of them children.
Genetic and environmental factors cause certain cells of our immune system (the T cells) to stop recognizing normal cells as normal, which is known as an autoimmune disease. The T cells think that these normal cells are actually intruders that need to be eliminated. This malfunction can occur because 1) the “educator cells” are not properly programming certain self-reactive T cells to be eliminated or remain unresponsive and/or 2) the T cells are no longer following the instructions of the “educator cells”. T1D is one of the most commonly known of these autoimmune diseases, in which T cells mistakenly attack insulin-producing cells (islet beta cells) in the pancreas. When these islet beta cells can’t produce enough insulin, blood sugars rise to dangerously high levels unless controlled with supplemental insulin. It is becoming clear that to achieve a durable remission of T1D, there needs to be a reprogramming of specific T cells.
Our objective is to engineer educator cells (generated from particular blood cells) to deliver a more complex set of instructions that will override the T cell malfunction. These new signals will: 1) teach the T cells that the islet cells are normal and should not be attacked, and 2) convert these same T cells into helpful “regulatory” T cells that reinforce the function of failing educator cells and counteract T cells that escaped reprogramming. This approach has multiple advantages over the use of conventional drugs by reprogramming only the relevant T cells and leaving the other T cells free to react against real intruders. Instead of using a conventional drug to treat symptoms of the underlying disease, our approach aims to use the body’s own immune system to correct the underlying malfunction which causes the disease. This represents an important step toward enhancing the efficacy of cell-based immunotherapy, a new form of personalized medicine with remarkable potential.
Why is this important?
We will engineer our educator cells to deliver specific signals, and we will measure how T cells respond to these signals. Not only can we see if T cells from a T1D patient ignore a particular signal (a signal that would not be ignored by T cells from a healthy individual), but we can also test combinations of signals that will make the T cells better understand the instructions they receive. Ultimately, these engineered educator cells will be used to reprogram malfunctioning T cells so that they stop attacking insulin-producing cells.
Who will benefit from the results of this project?
Therapy with engineered educator cells will be used to prevent T1D in high-risk individuals. This therapy may also help recently diagnosed T1D patients by stopping the autoimmune attack.
Remi Creusot, PhD Assistant Professor
The immune system is an incredibly fascinating organization and better understanding it has kept me going for many years. Many diseases are caused by immune disorders that we do not clearly understand. Over the years, I got to meet patients that gave a human dimension to this disease that I only knew through cells and molecules. Shortly after focusing my research on T1D, I became involved in fundraising for T1D research in general. Today, Consano gives me the possibility to showcase an aspect of my research that excites me, and hopefully to directly connect with the very people I want to help.
This project seeks to correct immune dysfunctions by using engineered white blood cells. In my lab, we are also interested in the origins of these dysfunctions, in particular, why the natural tolerance-inducing educator cells fail to function properly in T1D-prone individuals.
Education & Training
|2003 - 2007||Stanford University||Postdoctoral Fellow||Immunology|
|2002||University College London||PhD||Immunology|
|1998||University of Nancy (France)||MS||Microbiology|
|1996||University of Nancy (France)||BS||Biochemistry|
See where your dollars took us
Dear generous Supporters,
The fundraiser for this project ended about 6 months ago and although we raised 35% of the ultimate goal of $20,000, I think we did very well together. Here are some updates on our cell therapy project aimed at reprograming the T cells that cause Type 1 diabetes.
To remind you, the project aims at engineering a type of immune "instructor" cells to specifically engage (bait) pathogenic T cells and reprogram them so that they no longer attack insulin-producing beta cells, and if possible, convert them into becoming defenders for the beta cells. Although this is certainly possible, there is much to do to find the optimal way to engage only the pathogenic T cells without affecting those other immune cells that protect you from infections. Furthermore, finding the right "cocktail" of signals to make the reprograming as efficient as possible is one of our main goals. Your seed contributions helped us get started on two fronts:
1) We have already developed a new way to achieve optimal engagement in the mouse model of Type 1 diabetes, and with the data already accumulated, we will be submitting a patent application in the coming months. We will also publish data from this first phase in the coming months. We have proposed this approach and recently received two years of funding from the NIH to identify combinations of signals that would most efficiently reprogram pathogenic T cells upon engagement by instructor cells. We are so excited because you and Consano helped move us to this position where we have generated the bit of data we needed to convince the NIH that our work is worth funding.
2) We have started to explore ways to get human instructor cells to engage T cells, which will be needed in order to test the lessons we've learnt from the mouse model. We have dedicated another fraction of Consano funds to generate tools in that direction. The first type of tool we developed did not meet our expectations, and we have a second of tools to be tested in the future.
Do no hesitate to get in touch of us if you want more details or wish to support us further: firstname.lastname@example.org
Thank you so much!
First experiment is starting this week
We have spent the last two months gathering and preparing the materials and reagents for this project. This week, we will produce human dendritic cells and we will conduct our first series of manipulations on them, thanks to you!
An educational video explaining our approach will soon be available on Consano. Stay tuned!
The project is initiated
Your generous donations have allowed me to reach the first milestone of this fundraising effort. With the first check received from Consano, we will purchase the first reagents necessary to built the in vitro platform and enable human educator cells to form productive interaction with the target T cells. Once this interaction is validated, we will further modify the educator cells to reprogram the T cells to adopt a protective rather than destructive function.
Thank you again for your kind support, and please share the link for this page with your friends and relatives who may be interested to help in this effort. I will post an update early next year.
Wishing you a joyful and healthy holiday season.
Three days online...
... and we are already half way to starting the first phase of the project. Thank you so much for your contributions, no matter the amount, it is all meaningful and helpful. As the project makes progress, I will post updates to keep you informed.