Professor Robert A. Harris
Professor Robert A. Harris (Bob) was born in Harpenden in Southern UK in 1966. He conducted a Bsc.Hons undergraduate degree at Portsmouth Polytechnic, majoring in Parasitology in 1987. PhD studies at University College London studying innate immune agglutinins in Schistosoma host snail species with Terry Preston and Vaughan Southgate as supervisors culminated with a thesis defence in early 1991. A 2.5 year postdoc at the London School of Hygiene & Tropical Medicine in Paul Kaye’s research group ensued, with focus on understanding the intracellular fate of Leishmania spp. protozoans in macrophages. Bob was awarded a Wellcome Trust postdoctoral fellowship that permitted his relocation to the Karolinska Institutet (Stockholm, Sweden) in the spring of 1994. A postdoc period was spent split between the labs of Anders Örn and Tomas Olsson, in which he studied Trypanosoma cruzi and Trypanosoma bruceii protozoan proteins. Bob became an Associate Professor at the Karolinska Institutet in 1999, heralding his establishment as a PI. Bob started to work with autoimmune diseases in 1996 and began study of therapy using live parasite infections or parasite molecules. His research group has developed autoantigen-specific vaccines, defined the effects of post-translational biochemical molecules on autoantigenicity and developed a macrophage adoptive transfer therapy that prevents pathogenesis in several experimental disease models. He became Professor of Immunotherapy in Neurological Diseases in 2013. In recent years research focus has centred on understanding the immunopathogenesis of incurable neurodegenerative diseases, with particular emphasis on development of immunotherapies directed at microglial cells as potential therapeutic paradigms.
Bob Harris CV July 2020
ERIK HERLENIUS GROUP
Development of autonomic control
Immature or deficient autonomic control is a common problem in infants born at a premature age and is of central importance in apneas, secondary hypoxic brain damage and sudden infant death syndrome.
PER ERIKSSON GROUP
For better understanding of disturbances in respiratory control we study early development of cardiorespiratory control, brainstem neural networks and its associations with normal and pathological breathing. The conceptual change introduced by our recent data that endogenous prostaglandins are central pathogenic factors in respiratory disorders and the hypoxic response, open new diagnostic and therapeutic avenues that should significantly better the diagnostics and treatment of newborns and adult patients.
Inflammation is a major culprit in breathing disorders and we hypothesize that by using a newly developed urinary prostaglandin biomarker we can screen, detect and protect against inflammation related breathing disorders.
Our collaborative efforts enable us to move from a clinical problem to molecular understanding of the disease and studies are performed in patients, animal & in vitro models.
Our research is focused on the development of autonomic control with normal and paediatric patients as the target. Autonomic dysfunction in breathing and circulatory control often has its origin in neurodevelopment disorders. Furthermore, our basic research in developmental neuroscience how neural activity and stem cells form activity dependent networks is vital for the development of therapeutic interventions.
CENTER FOR MOLECULAR MEDICINE
Disorders of sex development, DSD
Congenital adrenal hyperplasia, CAH
AGNETA NORDENSKJÖLD GROUP
Two percent of all newborns have a congenital malformation. The parents often ask why this has happened, how it is treated, if there is a recurrence risk and what will happen in the future.
We study the molecular background of congenital malformations, especially disorders of sex development (hypospadias, uncertain sex at birth) and bladder exstrophy, when the child is born with an open urinary bladder. If the molecular diagnosis is determined the information about the child to the parents can be much better concerned further follow-up, prognosis and recurrence risk in the family. We also perform long-term follow up of adults that have been operated for these malformations and perform national register-based studies.
Our projects concern:
Molecular studies on DNA from families, mutation analysis of candidate genes in sporadic cases and families, arrayCGH and exome sequencing.
Clinical follow-up of adults with these diagnoses.
Register based studies on a national basis in order to identify different aspects of living with these diagnoses.
All results from these studies can easily directly be implemented in clinical practise.
Hypospadias, is a form of disturbed sex development in boys, when the meatus urethra is situated on the underside of the penis or in the perineum. The incidence in Sweden is 1 of 125 boys (Skarin et al 2014). The treatment is surgical. Hypospadia is a complex malformation arising due to an interaction between gene and environment. In our group we have studied monozygotic twins and also brothers to hypospadiac boys and could conclude that growth restriction is a factor in the pathogenesis of hypospadias, since it is the smallest of the twin/ brothers that get hypospadias. We have shown that the incidence in Sweden has increased to 1 in 125 boys and without a known cause.
Disorders of sex development, DSD
The first question parents get after the delivery of a child is whether it is a boy or a girl. For about 10-20 parents each year this is not possible to say without an anatomical, genetic and endocrine investigation. This investigation is performed urgently by the DSD-team at the hospital. Lately, the knowledge on the molecular background of DSD has increased very much and the child´s sex is easier to identify. Parents, patients and patient organisations ask for long-term follow up studies to improve information.
Congenital adrenal hyperplasia, CAH
CAH is an autosomal recessive inherited enzyme deficiency causing a lack of cortisol and aldosterone as well as an increased level of androgens. This affects 1 in 10 000 children every year and some get severe symptoms directly after birth. Girls will get virilised genitalia often before birth. Earlier studies have indicated a tomboy play-behaviour in girls with CAH that is also correlated to the severity of the mutation. We have performed a long-term follow up study in adult women with CAH concerning postoperative results, fertility and psychosexual and psychosocial issues including QoL. We found that choice of occupation and hobbies are more masculine than in controls and also correlated to the severity of the mutation, same as in children. We have shown a lower degree of fertility due to different causes, and that these women give birth to less boys than girls, the ”sex ratio” is 25:75. Finally we showed that voice characteristics are affected in women with CAH and that has not been investigated before.
Bladder exstrophy is a rare malformation when the urinary bladder is not closed and the child is born with an open bladder in the lower part of the abdomen. In Sweden around 3 children ae born every year with bladder exstrophy. They often have to be operated several times during up-bringing and also have medical check-ups regularly. The molecular background is not known, there is however an increased risk among relatives speaking for a genetic background. We were the first to identify that a duplication on chromosome 22 (22q11) is increasing the risk for getting bladder exstrophy and that a few % of bladder exstrophy cases have that chromosome aberration and also an increased risk for hearing loss (Lundin 2010). We have also identified a de novo mutation in a patient with bladder exstrophy and shown the effect of this mutation in a zebrafish model with a malformed cloaca (Körberg et al 2015).