Organ Health

Using the approach of noninvasive liquid biopsy, Signature’s research includes the study of organ systems and the health of organs themselves. By looking at both the cells that make up the form and function of the organ as well as their effects on the patient’s immune system, we retrieve epigenomic signatures that provide information specific to the patient’s body, such as its response to different treatments.

Our team is actively exploring solutions to the unique complications associated with organ transplants and long-term transplant survival. When a patient receives an organ transplant, new DNA is introduced into their body. Analyzing both the patient’s cell free DNA (cfDNA) and their donor-derived cell free DNA (dd-cfDNA) presents methods that could improve the sensitivity and specificity of post-transplant monitoring.

Renal Health

Renal allografts—also known as kidney transplants—are used to treat patients with end stage renal disease (ESRD). Despite advances in one-year allograft survival, long term survival is still a major concern in the organ transplant space. Premature graft loss generates several detrimental outcomes for the patient, including increased healthcare costs, poor quality of life, and an increased chance of mortality.

Late graft loss is primarily a result of cumulative immune-mediated damage that often goes undetected. The current gold standard for detecting graft rejection is an allograft biopsy, an invasive procedure that is both costly and introduces potential complications for the patient. 1

Organ Health - Renal

46.4%

of kidney transplants are lost by 10 years. 2

23,624

kidney transplants were performed in 2020.3

34.6%

of kidney transplant patients waitlisted between 2015-2017 waited over three years for transplant.3

Our Solution

Noninvasive Prenatal Screening (NIPS) offers an effective way to detect the potential of genetic conditions and complications of pregnancy. Using maternal plasma, we look for DNA methylation biomarkers to evaluate the fetal genetic health at a low risk to both the mother and baby.

Noninvasive prenatal screening is recommended for all pregnancies, regardless of maternal age or chromosomal risks (Rose et al., 2020). By screening for genetic conditions and abnormalities early on in the pregnancy, expectant mothers can collaborate with their care team to determine if additional diagnostics testing makes sense.

Lung Health

Lung transplantation is the treatment of choice for patients with end-stage lung disease (ESLD), but while transplant patient survival continues to improve, acute cellular rejection still occurs in up to 50% of patients within the first year following transplantation. If left untreated, ACR can cause significant decline in allograft function.

To detect ACR, lung transplant recipients commonly undergo multiple allograft biopsies for the first two years following the transplant. This invasive surveillance method is associated with various risks and is not always reliable enough to detect ACR for each patient.

Current noninvasive tests for detecting ACR are not sensitive enough to eliminate transbronchial biopsies, and they can not distinguish true allograft rejection from other transplant-related injuries.

Organ Health - Lung

8.9

The median survival rate for patients who surpass one-year lung transplant survival is 8.9 years.4

40%

of deaths beyond the first year of lung transplants are due to allograft failure.5

2,696

people were added to the lung transplant waiting list in 2020.6

Our Solution

Our team aims to employ a noninvasive approach to detecting ACR early by identifying diagnostically relevant signatures in fragments of the patient’s cell free DNA (cfDNA). By focusing on methylation patterns specific to cell type, this method also has the potential to differentiate between allograft rejection and other post-transplant complications. A noninvasive, early detection of ACR could decrease procedure-related risks/costs and improve quality of life for all lung transplant patients.

References

  • 1 Blencowe, H., Cousens, S., Chou, D., Oestergaard, M., Say, L., Moller, A., Kinney, M., Lawn, J., Born Too Soon Preterm Birth Action, Born Too Soon Preterm Birth Action Group, & the Born Too Soon Preterm Birth Action Group (see acknowledgement for full list). (2013). Born too soon: The global epidemiology of 15 million preterm births. Reproductive Health, 10(1), S2-S2. https://doi.org/10.1186/1742-4755-10-S1-S2
  • 2 Eskenazi, B. & Warner, M. L. Epidemiology of endometriosis. Obstet Gynecol Clin North Am 24, 235-258, doi:10.1016/s0889-8545(05)70302-8 (1997).
  • 3 Hassold, T., Chen, N., Funkhouser, J., Jooss, T., Manuel, B., Matsuura, J., Matsuyama, A., Wilson, C., Yamane, J. A., & Jacobs, P. A. (1980). A cytogenetic study of 1000 spontaneous abortions. Annals of Human Genetics, 44(2), 151-164. https://doi.org/10.1111/j.1469-1809.1980.tb00955.x
  • 4 McLeod, B. S. & Retzloff, M. G. Epidemiology of endometriosis: an assessment of risk factors. Clin Obstet Gynecol 53, 389-396, doi:10.1097/GRF.0b013e3181db7bde (2010).
  • 5 Rose, N. C., Kaimal, A. J., Dugoff, L., Norton, M. E., American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics, Society for Maternal-Fetal Medicine, & Committee on Genetics. (2020). Screening for fetal chromosomal abnormalities: ACOG practice bulletin, number 226. Obstetrics and Gynecology (New York. 1953), 136(4), e48-e69. https://doi.org/10.1097/AOG.0000000000004084
  • 6 Witt, W. P., Cheng, E. R., Wisk, L. E., Litzelman, K., Chatterjee, D., Mandell, K., & Wakeel, F. (2014). Preterm birth in the united states: The impact of stressful life events prior to conception and maternal age. American Journal of Public Health (1971), 104(2), 73.
  • 7 Nagaoka, S. I., Hassold, T. J., & Hunt, P. A. (2012). Human aneuploidy: Mechanisms and new insights into an age-old problem. Nature Reviews. Genetics, 13(7), 493-504. https://doi.org/10.1038/nrg3245