Thanks to you,
we see a brighter future for kids with SIOD.

Report prepared for Jessica and Kyle Davenport

November 2023

Jessica and Kyle, your generous commitment is changing lives.


Since 2017, your partnership with Lucile Packard Children's Hospital Stanford has brought hope to families facing rare genetic diseases.

Through the Kruzn for a Kure Foundation, you have given nearly $3 million to fuel scientific investigations that aim to improve treatments and create a better quality of life for kids with Schimke immuno-osseous dysplasia (SIOD). Your support launched a groundbreaking collaboration to make kidney transplants safer and more effective for kids like Kruz and Paizlee. Now, your continued generosity is advancing the next phase of SIOD research—developing and finding drug treatments.



We are deeply grateful for your vision, which is paving the way toward a brighter future for patients and their families. We are pleased to share the wonderful ways in which your generosity and determination are making an impact.

Your support has fueled the work of David B. Lewis, MD, chief of the Division of Allergy, Immunology, and Rheumatology in Stanford's Department of Pediatrics. Watch the video below to learn about the impact of your philanthropy directly from Dr. Lewis.

Creating a Human Cell Model of SIOD


Your funding has allowed Dr. Lewis' lab to begin unraveling the mystery of how SMARCAL1 protein deficiency leads to the clinical features of SIOD.

As you know, SIOD is caused by mutations of the SMARCAL1 gene. These mutations disrupt the normal DNA repair function of the SMARCAL1 protein, which somehow leads to cellular dysfunction of the kidney, immune system, growth plates, and blood vessels supplying the brain. While the exact mechanisms by which SMARCAL1 mutations lead to specific clinical features of SIOD are not fully understood, they likely involve the loss of some critical function of SMARCAL1 protein that is necessary to maintain these cell types in a healthy state.

Dr. Lewis aims to illuminate further the relationship between SMARCAL1 and SIOD using induced pluripotent stem cells (iPSCs). iPSCs have revolutionized regenerative medicine and biomedical research due to their remarkable ability to differentiate into various cell types found in the human body.

By reprogramming blood cells from patients, the Lewis Lab is generating iPSCs to create a human cell model that can successfully replicate the disease process that occurs in people who have SIOD. This model enables us to investigate the underlying causes of the disease and test potential treatments.

This advancement represents a huge step forward from previous efforts to create a disease model using genetically modified mice, which were not helpful. Even when mice had mutations in their SMARCAL1 gene similar to those found in SIOD patients, they did not develop any of the major clinical symptoms of SIOD seen in humans.

With the human cell model of SIOD we have today, we are closer than ever to our goal of developing therapies that will treat the range of symptoms caused by the SMARCAL1 mutation, including growth impairment, immune system dysfunction, kidney problems, and abnormal vascular function leading to migraines and seizures.

Your gifts are helping us understand and address migraine and the increased risk of stroke in children with SIOD.


Up to 40 percent of children with SIOD experience a neurovascular symptom called hemiplegic migraine, a rare form of migraine that can cause difficulty speaking, severe headache, and physical weakness on one side of the body. As you well know, sometimes the migraines can even lead to stroke. While it is clear these episodes are caused by a temporary decrease in blood flow to the brain followed by an increase in the diameter of the blood vessels, we do not yet know why they are more common in kids with SIOD—and whether they can be safely and effectively treated using existing migraine medications.

Because blood vessels play a pivotal role in the physiology of migraines, Dr. Lewis is looking at whether there are blood vessel abnormalities in SIOD that may contribute to these clinical problems. He believes there may be abnormalities in the endothelial cells, which form the inner lining of blood vessels. To test this theory, the Lewis Lab is using iPSCs to create endothelial cells and blood vessel-like structures to investigate, for the first time, how the SMARCAL1 protein influences either the differentiation of the blood vessels or their function.

Thanks to blood samples donated by your family, researchers in the Lewis lab already have early evidence that they are pursuing the right path. The total number of endothelial cells created with Paizlee's iPSCs was significantly lower compared to the number created by iPSCs from people without SIOD. This highlights that even in the making of the endothelial cells, the SMARCAL1 protein clearly plays an important role that the researchers had not anticipated.

Within the next six months, the Lewis Lab expects to have a clearer picture of the abnormalities in the endothelium that may account for the migraine headaches and risk of stroke associated with SIOD. Once they understand what is going wrong with the function of the endothelial cells, Dr. Lewis and his team hope to screen for potential drug treatments to prevent families from facing this frightening experience.



This first-of-its-kind research is fueled by collaborations across Stanford's campus, all made possible by you. Below, meet some of the brilliant researchers advancing this work.


Jordan Spatz, MD, PhD
Postdoctoral Scholar

Viswanath Gunda, PhD
Basic Research Scientist


Lewis Lab Developments

With your support, skilled molecular biologist Jordan Spatz, MD, PhD, joined the Lewis Lab in 2021. With a research focus on the SMARCAL1 protein, Dr. Spatz has moved forward studies using iPSCs to model cells and tissues that are affected in SIOD. In only a year's time, his efforts allowed the lab to develop a brand-new disease model for SIOD—a major task for a lab of this size. Dr. Spatz began his medical residency in the summer of 2022 and continues to be involved in this work virtually.

Dr. Spatz seamlessly passed this research project in 2022 to Viswanath Gunda, PhD, who is now directing the iPSC project. This work will provide new and important insights into the role of the SMARCAL1 protein in blood vessel problems such as migraines, transient ischemic attacks (brief interruptions of blood supply to the brain), and strokes and may help in devising new therapies for these complications.

Other studies may help determine whether SMARCAL1 protein deficiency acts to cause deficient function of the immune system and kidneys by a common mechanism shared with the blood vessels. The hope is that a single drug might be helpful for all of the various problems that result from SMARCAL1 deficiency.

Matt Porteus, MD, PhD
Director, Center for Definitive and Curative Medicine

Sridhar Selvaraj, PhD
Postdoctoral Fellow, Stem Cell Transplantation


Collaboration with the Porteus Lab

Your gifts have also enabled the Lewis Lab to collaborate closely with the lab of Matt Porteus, MD, PhD, director of the Center for Definitive and Curative Medicine (CDCM) at the Stanford School of Medicine. A pioneer in genome editing, he and his team aim to cure the incurable by investigating and developing stem cell and gene therapies for genetic diseases like SIOD.

The Porteus Lab has generously donated the time of senior postdoctoral fellow Sridhar Selvaraj, PhD, to help Dr. Gunda create new models of SIOD using iPSCs and CRISPR, a powerful technology that allows scientists to selectively change the DNA sequence of any gene.

This difficult process requires making a single change to the entire genome through precisely adding a stretch of DNA into exactly the right spot in the SMARCAL1 gene. Every person has two copies of each gene, one inherited from each parent. Editing both gene copies simultaneously during a single round of CRISPR, a process called biallelic modification, adds another layer of difficulty. In fact, the Porteus Lab is one of only a few labs capable of making biallelic edits. Dr. Gunda has been taught the process and is now routinely using this approach for the SIOD project.

With this technique, Dr. Gunda has created various cell lines (groups of cells that can be cultured and propagated in the lab) from your donated blood, Jessica. The cell lines only differ in how many copies they have of the SIOD-causing SMARCAL1 mutation—one, two, or none (normal SMARCAL protein).

Using this approach, they have taken iPSCs from a normal donor and modified them to allow the SMARCAL1 protein to be removed from the cells using a simple nontoxic drug. These approaches will allow our researchers to determine the impact of the complete loss of SMARCAL1 protein levels on the function of iPSCs and the tissues they are made into.

The initial experiments are now looking at the impact of the loss of SMARCAL1 protein on cell metabolism and the expression of other proteins with the goal of identifying drug interventions to prevent abnormalities in cell function from SIOD.


"Through state-of-the-art gene targeting, we can dial down the amount of SMARCAL1 protein in various organs.
This is a major breakthrough that will allow us to finally answer the question: What does this protein do that is so important, and how can we use this information to advance care for kids?"

David B. Lewis, MD

Professor of Pediatrics
Chief, Division of Allergy, Immunology, and Rheumatology
Stanford School of Medicine

Forging a Path
to Drug Discovery


Dr. Lewis' vision to identify a therapeutic treatment for SIOD within the next two years will require two important steps.

Publishing Novel Results

We must reduce SIOD's complex disease process to the point where researchers can use the CRISPR-edited cell lines to screen potential therapies. In the next year, once the preliminary findings from the cell models are robust and reproducible, Dr. Lewis aims to publish his lab's key findings.

This is a necessary and critical step in order for the team to apply for additional grants to supplement your incredible philanthropy and accelerate progress toward a therapy for SIOD.


Screening Potential Therapies

With grant support from institutions like the National Institutes of Health (NIH), the Lewis Lab will begin screening potential drug candidates for SIOD. To provide clinical benefits on a quicker timeline, the lab will start by screening existing compounds that have already been safely used in human clinical trials or that are FDA-approved, a process that Dr. Lewis estimates will take up to a year.

If an existing drug is not identified as an effective treatment for SIOD, the lab will join forces with academic and industry partners to pursue novel drug therapies.


Your philanthropy is creating a lasting ripple effect.


Once we identify the disease processes of SIOD, there is hope that the same processes will apply to many other diseases. If we can understand, for example, why blood vessels do not function normally in SIOD, we can apply that knowledge to treat other blood vessel disorders that elevate the risk of stroke. The same can be said for each of the organ systems affected by SIOD, including the kidneys, immune system, heart, and lungs. As we continue our pursuit of treatments for children like Kruz and Paizlee, the discoveries we make have the potential to improve the lives of countless kids and families at Packard Children's and beyond.



Thank you, Jessica and Kyle.

New discoveries and better treatments for SIOD are within reach, and your commitment is helping us write the next chapter for research and care.

We are deeply grateful for your leadership advancing this critical work. Because of you and the Kruzn for a Kure community, a brighter future is possible for children with SIOD and their families.

For more information, please contact

Michael Tomura
Associate Director, Major Gifts
(650) 461-9897 Michael.Tomura@LPFCH.org