Jacob Canick, PHD
Professor of Pathology & Laboratory Medicine
Pathology & Laboratory Medicine
Work: +1 401-453-7654
Beginning in the 1980s, our laboratory has studied secretory products of the human fetus and placenta as possible screening markers for prenatal identification of serious birth defects. We have been able to convert our findings into clinically important prenatal screening tests, now used throughout the world. In particular, our research has focused on prenatal screening markers and tests for fetal Down syndrome, trisomy 18, and various complications of pregnancy.
Research DescriptionBeginning in the mid 1980s, our laboratory has had a key part in the discoveries leading to major improvements in population-based prenatal screening for serious birth defects, particularly Down syndrome (trisomy 21).
In 1987 and 1988, we found that the maternal serum levels of estriol, the major estrogen of pregnancy, tended to be low in pregnancies affected by fetal Down syndrome. In 1988, in collaboration with colleagues at the Medical College of St. Bartholomew's Hospital in London and the Foundation for Blood Research in Maine, we showed that combining estriol measurement in the early second trimester with the measurement of two other pregnancy products, alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) would lead to a major improvement in the identification of pregnancies at high risk of fetal Down syndrome. Rather than only older pregnant women (35 years and older) being considered at sufficiently high risk to undergo the invasive diagnostic procedures (amniocentesis and cytogenetic analysis) needed to definitively identify affected pregnancies, for the first time the risk of pregnant women of all ages could be assessed with a high degree of accuracy. This so-called "triple test" detects about 70% of Down syndrome pregnancies (70% sensitivity) at a 5% screen positive rate (95% specificity), more than double the performance when using maternal age alone as the indicator of risk.
In addition to screening for Down syndrome, we showed in 1990 and that the triple test would be highly effective in identifying pregnancies at risk of Edwards syndrome (trisomy 18; a usually lethal aneuploidy that is about one-third as common as Down syndrome during the second trimester).
In 1994, we were the first to publish on an effective fourth marker in screening for Down syndrome, the placental hormone inhibin-A. The addition of inhibin-A to the triple test (resulting in the quad test) has increased the detection rate from 70% to 80%, without changing the specificity.
In recent years, new screening methods (the First Trimester and Integrated Tests) have been suggested, and our screening program has been directly involved in their validation and implementation in this country. The program served as the central laboratory and reporting site for the recently-completed multicenter NIH-funded intervention trial known as FASTER (First and Second Trimester Evaluation of Risk of Aneuploidy). Our research activities continue, with new emphasis on screening for major complications of pregnancy, such as preeclampsia and preterm delivery, as well as continued work on improving screening for Down syndrome and other chromosomal abnormalities.
Grants and Awards1998 Distinguished Scientist Award, Clinical Ligand Assay Society
2002 Election as a Fellow, National Academy of Clinical Biochemistry
2004 Traveling Lectureship Award from Canadian Society of Clinical Chemists
2005 Outstanding Speaker Award, American Association for Clinical Chemistry
AffiliationsThe Endocrine Society
American Association for Clinical Chemistry
National Academy of Clinical Biochemistry
Clinical Ligand Assay Society
American Society of Human Genetics
International Society for Prenatal Diagnosis
The Medical Screening Society
Funded ResearchRESEARCH GRANTS (GOVERNMENT/NON-PROFIT)
1979-1980 Principal Investigator: The William F. Milton Fund, Harvard University, Research grant: "Catechol estrogen biosynthesis in brain and liver of developing rat."
1979-1982 Principal Investigator: National Institute of Child Health and Human Development, Research Grant 1 RO1 HD12337: "Regulation of aromatization in hypothalamic cultures."
1981-1982 Principal Investigator: The Whitaker Health Science Fund, Grant for Harvard Medical School M.I.T. Collaborative Biochemical Research: "Catecholaminergic regulation of androgen metabolism in the perinatal rat brain: consequences for the development of sexual behavior." In collaboration with Dr. M.J. Baum of M.I.T.
1981-1987 Co-Investigator: National Institute of Child Health and Human Development, Research Grant1 RO1 HD 15595: "Testicular steroidogenesis in selected animal models." G.V. Callard, Principal Investigator
1983 Principal Investigator: The Rhode Island Foundation Herbert E. Hopkins Fund. Research Grant: "The characterization of steroidogenic enzymes in cultures of amniotic fluid cells."
1985-1988 Co-Investigator: National Institute of Child Health and Human Development, Research Grant 1 RO1 HD 21280: "Dehydroepiandrosterone sulfate as an ovarian prehormone." R.V. Haning, Principal Investigator
1989-1991 Co-Investigator: Maternal and Child Health Bureau, U.S. Dept. of Health and Human Services, to the New Engl. Regional Genet. Group, Project MCJ-25100306: "Regional demonstration project to test the feasibility of AFP, uE3, and hCG screening for Down syndrome in pregnant women of all ages." J.E. Haddow, Principal Investigator
1994-1995 Co-Principal Investigator: Maternal and Child Health Bureau, U.S. Dept. of Health and Human Services, to the New Engl. Regional Genet. Group: "Prenatal identification of placental sulfatase deficiency." L. Bradley, Co-Principal Investigator
1999-2004 Site Principal Investigator: National Institute of Child Health and Human Development, Research Grant 1 RO1 HD 38652: "First and second trimester evaluation of risk of aneuploidy (FASTER)." M.E. D'Alton, Principal Investigator
2001-2004 Site Principal Investigator: National Institute of Child Health and Human Development, Research Grant 1 RO1 HD 38940: "The feasibility of screening for Smith-Lemli-Opitz syndrome." J.E. Haddow, Principal Investigator
2004-2005 Site Investigator: National Institute of Child Health and Human Development, Research Grant 1 RO1 HD 38652: FASTER Supplemental Grant: "Hypothyroidism and pregnancy outcome: A FASTER trial study." M.E. D'Alton, Principal Investigator
RESEARCH GRANTS AND CONTRACTS (INDUSTRY)
1984 Travenol-Genentech Diagnostics, Cambridge, MA
1986 Kallestad Laboratories, Chaska, MN
1987 Kallestad Laboratories, Chaska, MN
1988 Amersham Clinical Diagnostics, Arlington Heights, IL
1993-2005 Diagnostic Systems Laboratories, Webster, TX
1995 Sanofi Diagnostics Pasteur, Chaska, MN
1996-1997 Chiron Diagnostics, Alameda, CA
2005-present Beckman Coulter Diagnostics, Fullerton, CA