WCMM clinical researchers
Wallenberg Molecular Medicine Clinical Researcher – Diabetes
The core of our research is to bridge the surprisingly under-explored gap between the “omics” of epidemiology (e.g. genomics, metabolomics and proteomics) and biological and clinical function. Thus, a major component our research is to enhance the understanding of causes to progressing diabetes and cardiovascular disease (CVD) where we invest large efforts in metabolomics and proteomics. However, a central issue is that we do not stop at finding metabolites/proteins and metabolomics/proteomic patterns associated with risk of progressing disease, but we also examine the importance of genetic predisposition behind such relationship to find causal association and we also aim to explore the underlying mechanisms (by in vivo/vitro experiments and even human trials if applicable).
Here we have already discovered two novel candidates in the amino acids isoleucine, phenylalanine, and tyrosine but also in dimethylglycine, which will be further tested to shed light on the biochemical underlying mechanisms. It is conceivable to assume that our causality assessment of biomarkers of disease will provide guidance on whether or not drug development targeted at the biomarker in question is worthy to pursue. Apart from this, we will generate substantial clinical value by accurately describing the utility of all known common and rare genetic diabetes and CVD susceptibility variants as well as metabolites and proteins in clinical diabetes and CVD risk prediction and risk stratification in some of the largest population based cohorts in the world.
Wallenberg Molecular Medicine Clinical Researcher – Cardiovascular System
Heart failure is the end-stage of all heart disease, characterized by inability of the heart to maintain sufficient output of blood for the demands of the body, and arguably constitutes the major unmet clinical need in cardiovascular medicine today.
In our research, we aim to improve understanding of the causes and mechanisms underlying heart failure, to identify novel therapeutic targets and facilitate individually tailored treatment strategies. My research group applies and integrates a range of omics tools to large cohorts with blood and heart tissues from heart failure cases, recipients of heart transplants and mechanical circulatory support, and the general population.
- More information about Gustav Smith in Lund University Research Portal
- Read about Gustav Smith and Anja Meissner in LUM magasin nr 6, 2017
Wallenberg Molecular Medicine Clinical Researcher – Nervous System
Our ultimate research vision is to discover, develop and implement novel neuroprotective and neurorestorative therapies for neurological disorders such as Parkinson’s disease, Huntington’s disease and stroke. My group works with translational research that is tightly linked to clinical research questions.
Our experimental focus is to understand neurovascular disease mechanisms. We examine the dysfunction of the neurovascular unit with a special focus on pericytes as key players in inflammation and neurodegeneration and as potential target cells for brain repair. We apply in vitro and in vivo disease modeling and utilize different patient samples.
We aim to identify new target cells facilitating brain repair and characterize novel restorative molecules for the above brain disorders. At the same time I am actively involved in clinical research with the focus on clinical implementation of stem cell and different growth factor therapies for Parkinson’s disease.
Wallenberg Molecular Medicine Clinical Researcher – Hematopoietic System
Our main goal is to improve outcome for the painful and fatal tumor disease, multiple myeloma (MM). To do this we will pursue three lines of research; i) use investigator initiated clinical trials to test prevention strategies and ii) to test new drug combinations and iii) investigate phagocyte subsets and functions during treatment and progression of MM. If successfull, this project will i) show that elimination of common subclinical infections could abrogate the MGUS clone and possibly prevent or decrease the risk of progression into MM ii) improve MM treatment and iii) gain knowledge of how phagocytes contribute to progression of MM. This will be of importance in a near future during the development of antibody based treatments against MM which depend on phagocyte immune functions, this could also lead to completely new treatment strategies targeting the MM supporting bone marrow miliue.
Wallenberg Molecular Medicine Clinical Researcher – Hematopoietic System
Hematopoietic cell transplantation (HCT) is often considered a last treatment resort for a number of serious diseases. At the Pediatrics Department in Lund, parental donors are often used in such setting, referred to as haploidentical (haplo-) HCT. In our research, we aim to study a number issues concerning haplo-HCT with the overall aim to increase efficacy and decrease treatment related complications.
First, in Haplo-HCT cells are transferred across large age boundaries; does this come at a price? Therefore, we study aging within our blood cell system, with a focus on hematopoietic stem cells. We study the mechanisms that drive these changes and aim to evaluate if haplo-HCT recipients present with signs a premature hematopoietic aging?
Second, as parental donors are only 50% HLA-identical, these children are at risk for graft-versus-host disease, whilst potentially benefitting from graft-versus-tumor actions. Future work will detail clinical outcome of such pediatric haplo-HCTs. Further, we will use a murine model to study hematological regeneration following haplo-HCT and evaluate how extended graft manipulation impacts graf-versus-tumor actions.
Wallenberg Molecular Medicine Clinical Researcher – Respiratory System
A considerable problem in lung transplantation is the shortage of donor lungs, and has resulted in deaths on the waiting list. A lot of improvements have been done considering donor management and organ preservation, still only approximately 20% of potential candidate lungs for transplantation are being transplanted. In addition chronic rejection - chronic lung allograft dysfunction (CLAD), primary graft dysfunction (PGD), and infections remains the major barrier to long-term success. The primary cause of death after LTx is CLAD. The development of CLAD is rare in the first year after LTx, but the rate increases quickly with cumulative incidence reported to be as high as 40 % to 80 % within the first five years. Bronchiolitis obliterans (BO) is the pathologic pattern of injury most commonly seen in lung transplant recipients with progressive loss of lung function. Distribution is often patchy in the lung parenchyma and is difficult to detect with trans-bronchial biopsy. Early CLAD diagnose detection, often increases the chance of survival, since early treatment might inhibit the development of CLAD, therefore it is a great need for finding new none invasive methods for early detection of CLAD but also for detection of PGD.
Our research group has a long-standing interest in lung transplantation (LTx) and the research focus has been on two main challenges in LTx, organ shortage and organ rejection. Our research group has focused on optimizing and improving marginal donor lungs using ex vivo lung perfusion (EVLP) on brain dead donors but also by using donation after cardio-circulatory determination of death (DCD) donors in the urge to increase the donor pole. Our research group has also focusing on finding early biomarkers for CLAD and PGD in exhaled air.
Wallenberg Molecular Medicine Clinical Researcher – Medical Imaging
Positron Emission Tomography with Computed Tomography (PET-CT) is a fast growing imaging modality and an important part of the evaluation of patients with cancer for assessment of the primary tumour, for lymph node staging and for detection of metastases. It can also be used for evaluation of inflammatory/infectious diseases, cardiac diseases and dementia. Recently, a novel generation of digital PET-CT scanners were developed, that will hopefully lead to improved diagnostic capacity, but this needs to be verified in studies. Current imaging techniques, including PET-CT, are challenged by time consuming manual analysis, lack of quantification and clinical validation. Objectively measured imaging biomarkers that reliably quantify the PET-tracer activity would therefore be important.
Our research group want to realize the true potential of PET-CT through two different projects: 1) To fully validate the new digital PET-CT scanners and 2) To use new artificial intelligence algorithms to develop novel PET-CT imaging biomarkers as indicators of prognosis and treatment efficacy in patients with cancer. Validated imaging biomarkers could transform future clinical care, clinical trials and drug discovery for cancer.
Wallenberg Molecular Medicine Clinical Researcher – Musculoskeletal System
Can children get rheumatic joint disease? Is it a life-long disease? Does my child really need all these drugs!!! These are the questions we hear every week when meeting families to children with newly diagnosed inflammatory joint disease.
To get a chronic disease will have a major impact on your day-to-day life and suddenly you are different… you need medications, repeated doctors’ visits… and you have pain.
-Why did I get this?!
In our research group, we try to answer these questions that patients and parents ask every day. We investigate the long-term prognosis and risk of comorbidities in children with inflammatory joint disease as well as the inflammatory pattern in the joint of these children. We will try to manipulate the immune-cells to switch from a pro-inflammatory state to a state of resolution and homeostasis.
Our overall aim is to improve the care of children with rheumatic diseases.
Wallenberg Molecular Medicine Clinical Researcher – Nervous System with Emphasis on Plasticity and Function
Manual daily activities require interactions between the peripheral and central nervous systems, which is obvious when an individual suffers a nerve injury, a neuropathy, or a stroke with subsequent impaired hand function. Hand amputees often use a prosthesis, which lack sensory feedback allowing only simple gripping.
This project has three aims: 1/ mapping cerebral plasticity, 2/ development of treatment strategies using guided plasticity for patients with nerve injury, neuropathy and stroke, and 3/ development of systems for sensory feedback and motor control of hand prosthesis.
The effects of the described conditions are examined in the peripheral nerve and in the brain, using advanced high (3T) and ultra-high (7T) magnetic resonance imaging (MRI) techniques, neurophysiology and clinical tests for development of treatment strategies, where the dynamic capacity of the brain, i.e plasticity, is guided to improve hand functions.
A modality-matched sensory feedback applicable in existing hand prosthesis is created with a new approach to control prosthetic hands. Control algorithms, based on intramuscular EMG or high-density surface EMG, are used to control modern, multi-degree of freedom, prosthetic hands.
Wallenberg Molecular Medicine Clinical Researcher – Cancer
Despite recent advances, there is still a substantial unmet medical need for novel cancer therapeutics. A new class of pharmacological compounds, based on RNA, open up new possibilities to specifically target numerous cancer cell vulnerabilities. Cytosolic delivery of the macromolecular RNA molecules is the biggest hurdle to translate these molecules into clinically useful drugs. Still, a few RNA based drugs have entered clinical use and delivery to certain human tissues, notably the liver and CNS, is possible. However, to reach other tissues, and in particular tumors, the delivery process has to be improved significantly.
In our lab we have two main focus areas: First, we develop methods to study the process of cytosolic delivery of RNA. In particular, we have developed high resolution microscopy methods to study RNA delivery in living cells. Second, based on the insights from these studies we are developing novel strategies to enhance RNA delivery to tumors. These efforts have the potential to specifically turn off driving cancer genes and ultimately halt disease progression.
Wallenberg Molecular Medicine Clinical Researcher – Medical Imaging
Imaging has a fundamental importance in medicine as it allows for non-invasive examination of both morphology and function. For translational science, imaging is a powerful tool, as the same imaging techniques can be used to evaluate treatment response in pre-clinical animal models, early human experiments, and lastly in large clinical studies. Medical image analysis is a research discipline where with help of computations one can identify and delimit structures in image volumes to quantify biological or physiological parameters. Image processing is a prerequisite to create objective quantitative analysis methods for diagnosis, clinical or preclinical research were the data comes from medical imaging.
In our research we develop novel methods and tools to process images. One research direction is towards full automation using machine learning to handle large study cohorts with tens of thousands of patients. Another research direction is precision medicine where imaging and image processing are used to develop patient specific models for surgical planning, combined with mathematical models to predict and optimize the outcome of the surgery.
Wallenberg Molecular Medicine Clinical Researcher - Translation of preclinical regenerative medicine into Advanced Therapy for Medicinal Products (ATMP)
Pulmonary hypertension (PH), high blood pressure in the lung, is a devastating condition where no curative treatment is available. It can be idiopathic (of unknown cause) or associated with other conditions. In children, PH associated with congenital heart disease is one of the most common types.
Ongoing projects in the group are aimed at understanding pathophysiological mechanisms in PH, with novel therapies as the ultimate goal. Our hypothesis is that the extracellular matrix, proteoglycans in particular, play important roles in the vascular remodeling seen in PH. Proteoglycans are however difficult to target pharmacologically. We will explore whether advanced therapy medicinal products (ATMPs) can be designed to alter either the production or the enzymatic turnover of the extracellular matrix. The aim is to restore a functional pulmonary vascular tree with lower pulmonary vascular resistance and pressure.
Efforts are also made to find biomarkers for disease burden, to be used for screening purposes and for evaluation of treatment effects. Synchrotron-based micro-CT is used as a tool for increased understanding of disease distribution in 3D space, in human tissue as well as in animal models.
In addition to the experimental studies we are involved in clinical registry-based studies in order to increase the understanding of the clinical needs and to contribute to more efficient use of the treatments available today.