Diego Forero was born in Bogotá, Colombia in 1980; he received his medical degree at the National University of Colombia in Bogotá (1998-2003). He had a strong interest in biomedical research since the early years at the medical school, during his final year he worked with the Neurosciences Research Group at the Institute of Genetics and after his graduation he worked there for two additional years in molecular neurogenetics (2004-2005).
He was one of the first 4 candidates selected for the VIB International PhD Program and he will receive his PhD degree in Biomedical Sciences at the University of Antwerp in Antwerp, Belgium (2006-2009), working at the Applied Molecular Genomics Group (VIB Department of Molecular Genetics) in molecular genetics and genomics of bipolar disorder and schizophrenia (with additional training at the VIB Laboratory of Developmental Genetics, Catholic University of Leuven and at the Unit of Animal Genomics, University of Liege).
He is currently participating in several research projects in molecular genetics of common neuropsychiatric disorders (bipolar disorder, schizophrenia, Alzheimer’s disease, Parkinson’s disease, attention deficit hyperactivity disorder, among others), in collaboration with several research groups around the world.
He has published several research papers in international journals, the majority of them as first and/or corresponding author; he has introduced the term “synaptogenomics” in the literature. Additionally, he has been speaker in different national and international scientific meetings and courses.
He participated in the creation of the first MSc program in Neurosciences in Latin America and was one of the founding members of the Colombian Association of Neurosciences. He is one of the editors of hum-molgen.org and has served as external reviewer for international journals and science funding organizations.
He is planning to return to the National University of Colombia to carry out further research in the genetic basis of common neuropsychiatric disorders.
Abstract: Through active reuptake of serotonin into presynaptic neurons, the serotonin transporter (5-HTT) plays an important role in regulating serotonin concentrations in the brain, and it is the site of binding for tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs). Therefore it has been hypothesized that this transporter is involved in the etiology of bipolar (BP) disorder. Inconsistent association study results for the SLC6A4 gene encoding 5-HTT reported in literature emphasize the need for more systematic and detailed analyses of this candidate gene. We performed an extensive analysis of SLC6A4 on DNA of 254 BPI patients and 364 control individuals from a Northern Swedish isolated population. This analysis consisted of a HapMap LD-based association study including three widely investigated polymorphisms (5-HTTVNTR, 5-HTTLPR, and rs3813034), a copy-number variation (CNV) analysis and a mutation analysis of the complete coding sequence and the 3'-UTR of SLC6A4. No single marker showed statistically significant association with BPI, nor did any of the haplotypes. In the mutation analysis 13 novel variants were detected, including 2 amino acid substitutions M389V and I587L, but these are probably not implicated in risk for BP. No deletions or duplications were detected in the CNV analysis. We conclude that variation in the SLC6A4 gene or its regulatory regions does not contribute to the susceptibility for BP disorder in the Northern Swedish population.
Abstract: In this paper, we review experimental advances in molecular neurobiology of Alzheimer's disease (AD), with special emphasis on analysis of neural function of proteins involved in AD pathogenesis, their relation with several signaling pathways and with oxidative stress in neurons. Molecular genetic studies have found that mutations in APP, PS1 and PS2 genes and polymorphisms in APOE gene are implicated in AD pathogenesis. Recent studies show that these proteins, in addition to its role in beta-amyloid processing, are involved in several neuroplasticity-signaling pathways (NMDA-PKA-CREB-BDNF, reelin, wingless, notch, among others). Genomic and proteomic studies show early synaptic protein alterations in AD brains and animal models. DNA damage caused by oxidative stress is not completely repaired in neurons and is accumulated in the genes of synaptic proteins. Several functional SNPs in synaptic genes may be interesting candidates to explore in AD as genetic correlates of this synaptopathy in a "synaptogenomics" approach. Thus, experimental evidence shows that proteins implicated in AD pathogenesis have differential roles in several signaling pathways related to neuromodulation and neurotransmission in adult and developing brain. Genomic and proteomic studies support these results. We suggest that oxidative stress effects on DNA and inherited variations in synaptic genes may explain in part the synaptic dysfunction seen in AD.
Abstract: BACKGROUND: Genetic analysis of human longevity may be useful for the understanding of molecular mechanisms implicated in age-related diseases. The molecular genetics of human longevity is largely unexplored in Latin American populations and other developing countries. METHODS: To explore the possibility of an association of common polymorphisms in two candidate genes and longevity in Colombia, we analyzed two polymorphisms in apolipoprotein E (APOE) and angiotensin-converting enzyme (ACE) genes in a sample of 538 Colombian subjects (18-106 years), using previously validated PCR-based methodologies. RESULTS: We found a significant decrease in ACE DD genotype (24 vs. 16%) between young and old subject groups (mean age: 45 vs. 77 years) (p = 0.03). The ACE DD genotype and D allele decrease was significant only in women. There were no differences for APOE polymorphism between young and old subjects. CONCLUSIONS: Our results are compatible with the expected age-related decrease of ACE DD genotype. Future studies examining functional single nucleotide polymorphisms (SNPs) in the ACE gene and its correlation with serum ACE activity in the older subjects and their younger relatives in this sample are warranted.
Abstract: In recent years, it has been proposed that synaptic dysfunction may be an important etiological factor for Alzheimer's disease (AD). This hypothesis has important implications for the analysis of AD genetic risk in case-control studies. In the present work, we analyzed common functional polymorphisms in three synaptic plasticity-related genes (brain-derived neurotrophic factor, BDNF Val66Met; catechol-O-methyl transferase, COMT Val158; ubiquitin carboxyl-terminal hydroxylase, UCHL1 S18Y) in a sample of 102 AD cases and 168 age and sex matched controls living in Bogotá, Colombia. There was not association between UCHL1 polymorphism and AD in our sample. We have found an initial association with BDNF polymorphism in familial cases and with COMT polymorphism in male and sporadic patients. These initial associations were lost after Bonferroni correction for multiple testing. Unadjusted results may be compatible with the expected functional effect of variations in these genes on pathological memory and cognitive dysfunction, as has been implicated in animal and cell models and also from neuropsychological analysis of normal subjects carriers of the AD associated genotypes. An exploration of functional variants in these and in other synaptic plasticity-related genes (a synaptogenomics approach) in independent larger samples will be important to discover new genes associated with AD.
Abstract: Analysis of genetic susceptibility factors for Alzheimer's disease (AD) in populations with different genetic and environmental background may be useful to understand AD etiology. There are few genetic association studies of AD in Latin America. In the present work, we analyzed polymorphisms in 3 candidate genes; the LDL receptor related protein-1, the microtubule-associated protein Tau and the serotonin transporter genes in a sample of 106 Colombian AD patients and 97 control subjects. We did not find a significant allelic or genotypic association with any of the three polymorphisms analyzed using different statistical analysis, including a neural network model or different sample stratifications. To date, APOE polymorphisms are the only genetic risk factors identified for AD in the Colombian population. It may be factible that future combination of high-throughput genotyping platforms and multivariate analysis models may lead to the identification of other genetic susceptibility factors for AD in the Colombian population.
