Research Project 1:
Little is known about biological changes that occur in the mother’s blood during and after pregnancy, and which genes are turned on/off to bring about these changes.
Dr. Jawaheer is leading an international collaborative research team to examine human gene expression* (i.e. genes “in action”) in the context of pregnancy in healthy women and women with rheumatoid arthritis** – to understand what genes are being turned on or off in the mother before, during and after pregnancy.
* Unlike “genetic testing” which shows what version of a gene is present, “gene expression” will inform us about how each gene behaves before, during and after pregnancy.
** What is rheumatoid arthritis (RA)?
RA is a chronic inflammatory disease of the joints that affects approximately 1 in every 100 adults worldwide, with women being affected 3 times more often than men. Why and how the disease occurs is still unknown. It is becoming increasingly clear, however, that it may the result of complex interactions between one’s genes and the environment that one has been exposed to. In a person with RA, the joints are “attacked” by the immune system, often resulting in destruction of cartilage and bone, leading to significant disability (due to pain and limited movement) and poor quality of life. Unfortunately, there is still no cure for RA, and although currently available medications can control the disease symptoms, these medications also have significant side-effects. Moreover, up to 30% of patients do not respond to them. Thus, RA remains one of the leading causes of chronic impairment worldwide, among people of all cultures in all countries.
Our research will enable us to understand (a) what normal biological changes occur during pregnancy1 and after child-birth, (b) why women are at higher risk of developing some cancers (breast cancer) and autoimmune diseases (e.g. thyroid disease, rheumatoid arthritis) in the months following child-birth. Furthermore, the data generated from the healthy women can be used as a “reference” by other researchers to understand what is different in abnormal pregnancies.
Our data provide snapshots of the maternal “environment” that the fetus is exposed to in each trimester of pregnancy. These data will allow us to examine the patterns of maternal genes that are turned on/off during pregnancy in relation to:
(a) birth outcomes2, (b) long-term health of the children born3.
Women with some autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS) often experience (i) a natural improvement of their symptoms during pregnancy, and (ii) a predictable return of the symptoms 3-6 months after child-birth. Why this happens is unknown. Our research will generate new knowledge regarding why the natural improvement of symptoms during pregnancy and the flare after child-birth occur in RA.
Research Project 2:
Pharmacogenomics of anti-TNF Therapy in Rheumatoid Arthritis
The goal of this research is to identify genetic factors that affect response to anti-TNF biologic drugs among patients with RA4, and to gain a better understanding why some patients respond better than others.
Although anti-tumor necrosis factor (TNF) drugs can be very effective in controlling the progression of RA into more severe forms, approximately 30% of patients do not respond to them. In addition, these drugs are associated with risks of serious side effects and are very costly. Because there are no known tests to predict how a patient will respond, currently these drugs are given to patients indiscriminately. This approach results in non-responders being exposed to serious health risks from the side effects of drugs from which they will not benefit. There are also enormous healthcare costs involved in treatment of any resulting side effects and adverse events. Hence, the ability to predict who is likely to be a good responder will allow treatment to be targeted to those patients, enabling a precision medicine approach for anti-TNF therapy in RA.
- Mittal A, Pachter L, Nelson JL, Kjærgaard H, Smed MK, Gildengorin VL, Zoffmann V, Hetland ML, Jewell NP, Olsen J, Jawaheer D. Pregnancy-induced changes in systemic gene expression among healthy women and women with rheumatoid arthritis. PLoS One. 2015 Dec 18;10(12): e0145204. Article
- Rom AL, Wu CS, Olsen J, Kjaergaard H, Jawaheer D, Hetland ML, Vestergaard M, Mørch LS (2014). Fetal growth and preterm birth in children exposed to maternal or paternal rheumatoid arthritis. A nationwide cohort study. Arthritis Rheumatol. 66(12):3265-73. Article.
- Rom AL, Wu CS, Olsen J, Jawaheer D, Hetland ML, Ottesen B, Mørch LS. Parental rheumatoid arthritis and long-term child morbidity: a nationwide cohort study. Ann Rheum Dis. 2015 Dec 23. pii: annrheumdis-2015-208072. doi: 10.1136/annrheumdis-2015-208072. [Epub ahead of print]
- Honne K, Hallgrímsdóttir I, Wu C, Sebro R, Jewell NP, Sakurai T, Iwamoto M, Minota S, Jawaheer D. A longitudinal genome-wide association study of anti-tumor necrosis factor response among Japanese patients with rheumatoid arthritis. Arthritis Res Ther. 2016: 18(1):12. Article.
Friday, April 17, 2020 1:15 PM