Sie Fellowship

Sie Fellowship Blog: Maria Lo

Anonymous — Mon, 21 Oct 2019 19:38:11 +0000

Sie Fellowship Blog: Maria Lo Anonymous (not verified) Mon, 10/21/2019 - 13:38

Maria Lo

Blog post

9/30/19

I am very thankful to the Sie Foundation and the Linda Crnic Institute for the opportunity to perform research aimed at enhancing the lives of individuals with Down Syndrome, or Trisomy 21. The Sie Fellowship has provided me with the resources to apply my skillset to a very important area of research and allowed me to become part of a dynamic community highly motivated to tackling the many health challenges faced by individuals with Down Syndrome. I have been working as a postdoctoral fellow in Dr. Amy Palmer’s lab at the BioFrontiers Institute on understanding how an essential micronutrient, Zn²⁺, influences cell proliferation. In a forthcoming paper, I have described how Zn²⁺ deficiency influences human cell growth on a cell-by-cell basis. This work helped lay the groundwork for my studies in trisomy 21 cells.

Interestingly, there are several reports in the literature where individuals with Down Syndrome had decreased levels of Zn²⁺. Importantly, Zn²⁺ deficiency can cause growth and developmental defects and, at the cellular level is known to reduce growth and proliferation. However, how these Zn²⁺ deficiencies influence cell growth in trisomy 21 cells is not understood. I am exploring how potential Zn²⁺ deficiencies in individuals with Down Syndrome influences their cell growth. At a basic level, a series of steps called the cell cycle controls how cells grow and divide. Proper control of each step in the cell cycle is critical for tissue development and homeostasis. In humans, dysregulation of the cell cycle can give rise to diseases such as neurodegeneration, characterized by a loss in proliferation, or cancer, characterized by uncontrolled proliferation and an inability to respond to cues otherwise triggering controlled exit from the cell cycle. To understand why individuals with Down Syndrome have a different spectrum of these proliferative disorders, I wanted to determine how the cell cycle is different in cells from individuals with Down Syndrome compared to typical individuals. This is an area that has been touched upon by various scientists, but a comprehensive analysis of the cell cycle at a single-cell level is lacking. I found that a critical protein controlling normal progression of the cell cycle is misregulated in trisomy 21 cells, suggesting individuals with Down Syndrome have a defect in proper control of the cell cycle. I am exploring how this fundamental difference changes the response of cells to conditions of stress such as serum starvation and Zn²⁺ deficiency. With the remainder of my time as a Sie Fellow, I am working to further elucidate key changes in the cell cycle pathway that differ in individuals with Down Syndrome. I hope these analyses will help elucidate how cell cycle switches are impaired in trisomy 21 cells, and ultimately how these changes might contribute to the altered cancer and neurobiology profile inherent to Down Syndrome.

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Sie Fellowship Blog: Joseph Cardiello

Anonymous — Mon, 21 Oct 2019 19:33:06 +0000

Sie Fellowship Blog: Joseph Cardiello Anonymous (not verified) Mon, 10/21/2019 - 13:33

Joseph Cardiello
Year 1 blog update
Year 1: October 1, 2018-September 1, 2019
Sie Foundation Fellowship

The first year of being funded by the Sie Foundation Postdoctoral Fellowship has been quite eventful as I set out to learn a host of new wet lab techniques, analysis methods, and a new biological perturbation to wrap my head around: trisomy 21. My favorite current project focuses on whether cells with three copies of chromosome 21 display more RNA level variations than cells with two copies. We hypothesized that having a third chromosome 21 may complicate the ability of cells to evenly express RNA levels across a cell population. I began testing this hypothesis by generating single cell RNA-seq data for paired cell lines, derived from white blood cells of two brothers: one who is trisomic for chromosome 21 and another who is not. The data for this project is relatively new and I am still consulting with various researchers about how best to statistically test these hypotheses. So far it appears that cells with trisomy 21 may display increased variability in some RNA levels, but these results are preliminary and still need to be robustly tested statistically and followed up with more experiments.

Each of my initial projects have required the use of large data processing pipelines, bioinformatic analyses and custom data analysis, all skills that I’ve been working towards acquiring in the Dowell Allen lab. To this end, upon joining the Dowell Allen lab I learned to process data on the BioFrontiers Fiji distributed computer. I also learned to use faster data processing pipelines developed by members of the Dowell Allen lab. Finally, I began learning to do some of my own coding and analysis using the python coding language. The learning curve for this analysis has been steep, but it’s been a welcome challenge as the ability to write custom code is hugely rewarding in opening up the number of scientific questions I can ask of my data.

I’ve also taken this year to learn more about science education and to work on my writing skills. This summer I took an introduction to evidence-based teaching course offered at CU �鶹ӰԺ and attended by postdocs from around the country. The course introduced a wide variety of active learning methods that I hope to apply to future teaching experiences. I also taught one day of the short-read workshop class that the Dowell Allen lab holds each year to give researchers an introduction to sequencing analysis. It was an exciting challenge to make this tutorial on the analysis of ChIP-seq and ATAC-seq, two next generation sequencing methods, interactive and accessible to the wide range of students in the course. I also mentored a graduate student in the lab, and she subsequently joined our lab. Finally, as a team, with Robin Dowell, Mary Allen, and another postdoc in our lab, Gilson Sanchez, I helped write a review paper on enhancer RNAs. This has been a great first year on this fellowship and I can’t wait to see what exciting results my projects produce over the next year.

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Sie Fellows focused on quality of life in Down syndrome

Anonymous — Thu, 10 Jul 2014 06:00:00 +0000

Sie Fellows focused on quality of life in Down syndrome Anonymous (not verified) Thu, 07/10/2014 - 00:00

BioFrontiers

Mary Allen holds up a valentine sent to her from a childhood friend. It sits in her cubicle where she is hard at work tearing apart genomic data looking for patterns. This friend, who has Down syndrome, is part of the reason that Allen, a postdoctoral researcher in Robin Dowell’s lab at the BioFrontiers Institute, became interested in studying aneuploidy. Aneuploidy means that cells have too many, or too few, of one or more chromosomes. In the case of Down syndrome, there is an extra copy of chromosome 21. Allen is exploring what makes people with this extra chromosome survivors.

“Down syndrome is actually not all that survivable,” says Allen. “Only 25 percent of embryos with three copies of chromosome 21 survive to live birth. These people who are surviving and living long lives have something in their DNA—from their genetic background—that is helping them.”

Down syndrome is the most commonly occurring chromosomal condition and more than 400,000 people in the United States are currently living with it. Allen is right about them being survivors. According to the Global Down Syndrome Foundation, life expectancy for people with the syndrome has increased dramatically from 25 years in 1983 to 60 years now, due in part to better educational programs, health care and support from families and communities.

Allen is taking genetic sequencing data from people with Down syndrome and their parents to understand how that extra copy of chromosome 21 puts this population at higher risk for health issues such as heart defects, thyroid conditions, leukemia, Alzheimer’s disease, and respiratory and hearing problems. She is also trying to understand why they are at lower risk for heart attack, stroke, and solid tumor cancers. Allen isn’t out to find a cure for Down syndrome. Her goal is to find what in their DNA is helping these survivors, and how can we design targeted molecular therapy to help them have better lives.

“Once you have had a friend with Down syndrome, stopping the occurrence of the syndrome isn’t on the table,” says Allen. “They are just such great people.”

Allen recently was awarded a Sie Foundation Postdoctoral Fellowship to continue her Down syndrome research for the next two years. This fellowship was created under the Anna and John J. Sie Endowment Fund for the BioFrontiers Institute, which is targeted specifically at funding research to prevent the cognitive and medical ill effects associated with the extra chromosome 21. The fellowship is offered as a collaboration between BioFrontiers and the Linda Crnic Institute for Down Syndrome at the University of Colorado, Anschutz Medical Campus.

The BioFrontiers Institute also awarded Sie Fellowships to Geertruida Josien Levenga of CU-�鶹ӰԺ’s Institute of Behavioral Genetics and to Alfonso Garrido-Lecca of CU-�鶹ӰԺ’s Department of Molecular, Cellular and Developmental Biology. Dr. Levenga is a neuroscientist whose research holds promise for ameliorating the seizures that afflict so many individuals with Down syndrome. Dr. Garrido-Lecca will test the hypothesis that alteration of microRNA levels in individuals with Down syndrome contributes to some of their health challenges.

Dr. Allen sees the new fellowship as welcome news for her work. Research funding for Down syndrome has always been extremely low. The National Institutes of Health in 2012 allocated only $50 in research funding per person living with the condition, versus $270 for Fragile X research, $329 for multiple sclerosis research and $2,867 for cystic fibrosis research. Individuals with Down syndrome have special health needs, like heart conditions and decreased immunity, which can be helped by further research. In addition, since Alzheimer’s disease, leukemia, low muscle tone and weight gain are seen at a high incidence in people with Down syndrome, researching the syndrome may lead to treatments for these associated disorders in the broader population.

“Research on the smaller ear canals of people with Down syndrome is now helping people who suffer from deafness and other auditory disorders,” says Allen. “Unlocking the cellular processes behind one disorder can help us with so many others.”

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BioFrontiers launches Sie Post-doctoral Fellowship Program

Anonymous — Thu, 10 Jul 2014 06:00:00 +0000

BioFrontiers launches Sie Post-doctoral Fellowship Program Anonymous (not verified) Thu, 07/10/2014 - 00:00

BioFrontiers

Research will focus on improving the lives of people with Down syndrome

The BioFrontiers Institute at the University of Colorado launched its inaugural Sie Post-doctoral Fellowship Program in affiliation with the Linda Crnic Institute for Down Syndrome on the Anschutz Medical Campus. The program will fund three post-doctoral researchers, Sie Fellows, who will focus on research that will improve the lives of individuals with Down syndrome.

The Sie Fellows research is co-funded by the BioFrontiers Institute and the Anna and John J. Sie Foundation. Every two years, three Sie Fellows will be selected from a competitive grant process and will receive between $71,000 and $85,000 a year for two years.

Nobel laureate and Director of the BioFrontiers Institute Thomas Cech, BioFrontiers Chief Scientific Officer (CSO) Leslie Leinwand, and Executive Director of the Crnic Institute Tom Blumenthal were key in assessing the 44 applicants prior to deciding on the inaugural three recipients: Mary Allen of CU-�鶹ӰԺ’s Department of Molecular, Cellular and Developmental Biology (MCDB), Geertruida Josien Levenga of CU-�鶹ӰԺ’s Institute of Behavioral Genetics, and Alfonso Garrido-Lecca of MCDB.

“The projects being carried out by the Sie Fellows are key to significantly improving the lives of people with Down syndrome and to eradicating the medical and cognitive ill effects associated with the condition,” said Leinwand. “The support of early-stage post-doctoral fellows is crucial in any research operation, and these awards make it possible for faculty to increase their commitment to this important cause.”

BioFrontiers officially earned institute status in 2011 and brings together faculty members from the life sciences, physical sciences, computer science and engineering with the passion and skills needed to research across traditional disciplines and tackle difficult medical issues.

“The fact that there were 44 applicants for three awards underscores how exciting research for Down syndrome is, and the potential for real scientific contribution,” said Blumenthal. “With our Supergroup of 60 scientists working on Down syndrome and meeting monthly from different disciplines and different schools, we are truly making a difference for this special population and their families.”

“The Global Down Syndrome Foundation is pleased to add these outstanding researchers to our future portfolio of research we aim to fund and advocate for. Their research is already so relevant,” said Michelle Sie Whitten, executive director of the Global Down Syndrome Foundation, the fundraising and advocacy arm of the Crnic Institute.

Allen’s research involves genetic sequencing data from people with Down syndrome and their parents to understand how an extra copy of chromosome 21 puts people with Down syndrome at higher risk for health issues such as heart defects, thyroid conditions, leukemia, Alzheimer’s disease, and respiratory and hearing problems, but at lower risk for heart attack, stroke and solid-tumor cancers.

Levenga, who is a neuroscientist, is conducting research into ameliorating the seizures that afflict many people with Down syndrome.

Garrido-Lecca will test the hypothesis that alteration of microRNA levels in people with Down syndrome contributes to some of their health challenges.

Down syndrome is the most commonly occurring chromosomal condition, affecting one out of every 691 live births in the U.S., according to the Centers for Disease Control and Prevention. Because of the end of widespread institutionalization, better medical care, improved access to education and greater societal inclusion, people with Down syndrome are living longer and more productive lives, with the average life span increasing from 25 years in 1983 to 60 years today.

�鶹ӰԺ the BioFrontiers Institute

At the University of Colorado BioFrontiers Institute, researchers from the life sciences, physical sciences, computer science and engineering are working together to uncover new knowledge at the frontiers of science and partnering with industry to make their discoveries relevant.

�鶹ӰԺ the Linda Crnic Institute for Down Syndrome

The Linda Crnic Institute for Down Syndrome is the first medical and research institute with the mission to provide the best clinical care to people with Down syndrome, and to eradicate the medical and cognitive ill effects associated with the condition. Established in 2008, the Crnic Institute is a partnership between the University of Colorado School of Medicine, the University of Colorado at �鶹ӰԺ and Children’s Hospital Colorado. Headquartered on the Anschutz Medical Campus in Aurora, the Crnic Institute includes the Anna and John J. Sie Center for Down Syndrome at Children’s Hospital Colorado. It partners both locally and globally to provide life-changing research and medical care for individuals with Down syndrome. The Crnic Institute is made possible by the generous support of the Anna and John J. Sie Foundation, and relies on the Global Down Syndrome Foundation for fundraising, education, awareness and government advocacy. It is a research and medical-based organization without political or religious affiliation or intention.

�鶹ӰԺ the Global Down Syndrome Foundation

The Global Down Syndrome Foundation is a public nonprofit 501(c)(3) dedicated to significantly improving the lives of people with Down syndrome through research, medical care, education and advocacy. Established in 2009, Global has the primary focus of supporting the Linda Crnic Institute for Down Syndrome, the first academic home in the U.S. committed to research and medical care for people with the condition. Fundraising and government advocacy that corrects the alarming disparity of national funding for people with Down syndrome is a major short-term goal. Global organizes the Be Beautiful Be Yourself Fashion Show – the single-largest annual fundraiser benefiting people with Down syndrome. Global also organizes and funds many programs and conferences, including the Dare to Play Football and Cheer Camps, Global Down Syndrome Educational Series, and the Be Beautiful Be Yourself Dance Class. Global is an inclusive organization without political or religious affiliation or intention.

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