About

Roberto Colangeli, PHD, BSc, is an Assistant Professor in the Department of Medicine at Rutgers New Jersey Medical School, working within the field of Medical Science. He received his Ph.D. in Microbiology and Infectious Diseases from La Sapienza University in Rome, Italy, and his BSc from Instituto Tecnico Industriale L. Lagrange in Italy. His research focuses on understanding the molecular mechanisms that enable Mycobacterium tuberculosis to develop resistance to antibiotics, with particular emphasis on antibiotic tolerance as a precursor to resistance. Dr. Colangeli has discovered several genes involved in antibiotic tolerance in M. tuberculosis, including the global transcriptional regulator lsr2, which regulates efflux pumps involved in tolerance to isoniazid (INH). He has initiated projects to delete efflux pumps in M. tuberculosis, hypothesizing their importance in intrinsic resistance, and maintains a collection of over 70 pump mutants for testing their response to antibiotics and survival in macrophages. His background includes work at the Italian National Institute of Health, the Public Health Research Institute in NYC, and Albert Einstein College of Medicine. He also serves as a consultant on bacterial infections for a European Union project.

Research topics

• Immunology
• Environmental health
• Psychology
• Microbiology
• Psychoanalysis
• Medicine
• Biology
• Genetics

Selected publications

• Psychoanalysis and Epigenetics

  2022-07-04

  book-chapter1st authorCorresponding

  This chapter will address the correlation between environmental conditions, psychological trauma, and changes in DNA structure. Traditionally, human behaviors have been explained using either biological or psychoanalytic approaches. In recent years, a new branch of genetics (epigenetics) has emerged to study the interaction between human behavior and changes in DNA expression. It has been shown that epigenetic modifications respond to environmental stimuli, and they are also reversible. Thus, epigenetics represents a bridge between biology and psychoanalysis. In this new understanding, modifications of human behavior are correlated with alterations to the DNA structure. Therefore, psychoanalytic treatment, which has been shown to treat several mental disorders effectively, is also able to regulate DNA changes caused by environmental stress. This concept is particularly significant in the physiological heritability of psychological trauma. Healing psychological trauma in an individual not only heals that individual, but also preempts the passage of that trauma at the DNA level to the children of the individual. This chapter will explore how psychoanalysis can influence epigenetic changes in patients that can in turn play a significant role in reducing the intergenerational transmission of trauma for future generations.

  PublisherDOI

• Mycobacterium tuberculosis progresses through two phases of latent infection in humans

  Nature Communications · 2020 · 78 citations

  1st authorCorresponding
  • Biology
  • Immunology
  • Microbiology

  Little is known about the physiology of latent Mycobacterium tuberculosis infection. We studied the mutational rates of 24 index tuberculosis (TB) cases and their latently infected household contacts who developed active TB up to 5.25 years later, as an indication of bacterial physiological state and possible generation times during latent TB infection in humans. Here we report that the rate of new mutations in the M. tuberculosis genome decline dramatically after two years of latent infection (two-sided p < 0.001, assuming an 18 h generation time equal to log phase M. tuberculosis, with latency period modeled as a continuous variable). Alternatively, assuming a fixed mutation rate, the generation time increases over the latency duration. Mutations indicative of oxidative stress do not increase with increasing latency duration suggesting a lack of host or bacterial derived mutational stress. These results suggest that M. tuberculosis enters a quiescent state during latency, decreasing the risk for mutational drug resistance and increasing generation time, but potentially increasing bacterial tolerance to drugs that target actively growing bacteria.

  PublisherOA PDFDOI

• Bound Together: How Psychoanalysis Diminishes Inter-generational DNA Trauma

  The American Journal of Psychoanalysis · 2020 · 6 citations

  1st authorCorresponding
  • Psychology
  • Psychoanalysis
  PublisherDOI

• Bacterial Factors and Relapse after Tuberculosis Therapy

  New England Journal of Medicine · 2019-01-09 · 1 citations

  letter1st authorCorresponding
  PublisherDOI

• Bacterial Factors That Predict Relapse after Tuberculosis Therapy

  New England Journal of Medicine · 2018-08-29 · 157 citations

  articleOpen access1st authorCorresponding

  BACKGROUND: Approximately 5% of patients with drug-susceptible tuberculosis have a relapse after 6 months of first-line therapy, as do approximately 20% of patients after 4 months of short-course therapy. We postulated that by analyzing pretreatment isolates of Mycobacterium tuberculosis obtained from patients who subsequently had a relapse or were cured, we could determine any correlations between the minimum inhibitory concentration (MIC) of a drug below the standard resistance breakpoint and the relapse risk after treatment. METHODS: Using data from the Tuberculosis Trials Consortium Study 22 (development cohort), we assessed relapse and cure isolates to determine the MIC values of isoniazid and rifampin that were below the standard resistance breakpoint (0.1 μg per milliliter for isoniazid and 1.0 μg per milliliter for rifampin). We combined this analysis with clinical, radiologic, and laboratory data to generate predictive relapse models, which we validated by analyzing data from the DMID 01-009 study (validation cohort). RESULTS: In the development cohort, the mean (±SD) MIC of isoniazid below the breakpoint was 0.0334±0.0085 μg per milliliter in the relapse group and 0.0286±0.0092 μg per milliliter in the cure group, which represented a higher value in the relapse group by a factor of 1.17 (P=0.02). The corresponding MIC values of rifampin were 0.0695±0.0276 and 0.0453±0.0223 μg per milliliter, respectively, which represented a higher value in the relapse group by a factor of 1.53 (P<0.001). Higher MIC values remained associated with relapse in a multivariable analysis that included other significant between-group differences. In an analysis of receiver-operating-characteristic curves of relapse based on these MIC values, the area under the curve (AUC) was 0.779. In the development cohort, the AUC in a multivariable model that included MIC values was 0.875. In the validation cohort, the MIC values either alone or combined with other patient characteristics were also predictive of relapse, with AUC values of 0.964 and 0.929, respectively. The use of a model score for the MIC values of isoniazid and rifampin to achieve 75.0% sensitivity in cross-validation analysis predicted relapse with a specificity of 76.5% in the development cohort and a sensitivity of 70.0% and a specificity of 100% in the validation cohort. CONCLUSIONS: In pretreatment isolates of M. tuberculosis with decrements of MIC values of isoniazid or rifampin below standard resistance breakpoints, higher MIC values were associated with a greater risk of relapse than lower MIC values. (Funded by the National Institute of Allergy and Infectious Diseases.).

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• Author Correction: The FAAH inhibitor URB597 suppresses hippocampal maximal dentate afterdischarges and restores seizure-induced impairment of short and long-term synaptic plasticity

  Scientific Reports · 2018-03-09

  erratumOpen access1st authorCorresponding

  A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

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• The mycobacterial iron‐dependent regulator <scp>IdeR</scp> induces ferritin (<scp><i>bfrB</i></scp>) by alleviating <scp>L</scp>sr2 repression

  Molecular Microbiology · 2015-08-13 · 40 citations

  articleOpen access

  Emerging evidence indicates that precise regulation of iron (Fe) metabolism and maintenance of Fe homeostasis in Mycobacterium tuberculosis (Mtb) are essential for its survival and proliferation in the host. IdeR is a central transcriptional regulator of Mtb genes involved in Fe metabolism. While it is well understood how IdeR functions as a repressor, how it induces transcription of a subset of its targets is still unclear. We investigated the molecular mechanism of IdeR-mediated positive regulation of bfrB, the gene encoding the major Fe-storage protein of Mtb. We found that bfrB induction by Fe required direct interaction of IdeR with a DNA sequence containing four tandem IdeR-binding boxes located upstream of the bfrB promoter. Results of in vivo and in vitro transcription assays identified a direct repressor of bfrB, the histone-like protein Lsr2. IdeR counteracted Lsr2-mediated repression in vitro, suggesting that IdeR induces bfrB transcription by antagonizing the repressor activity of Lsr2. Together, these results elucidate the main mechanism of bfrB positive regulation by IdeR and identify Lsr2 as a new factor contributing to Fe homeostasis in mycobacteria.

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• Whole Genome Sequencing of Mycobacterium tuberculosis Reveals Slow Growth and Low Mutation Rates during Latent Infections in Humans

  PLoS ONE · 2014-03-11 · 93 citations

  articleOpen access1st author

  Very little is known about the growth and mutation rates of Mycobacterium tuberculosis during latent infection in humans. However, studies in rhesus macaques have suggested that latent infections have mutation rates that are higher than that observed during active tuberculosis disease. Elevated mutation rates are presumed risk factors for the development of drug resistance. Therefore, the investigation of mutation rates during human latency is of high importance. We performed whole genome mutation analysis of M. tuberculosis isolates from a multi-decade tuberculosis outbreak of the New Zealand Rangipo strain. We used epidemiological and phylogenetic analysis to identify four cases of tuberculosis acquired from the same index case. Two of the tuberculosis cases occurred within two years of exposure and were classified as recently transmitted tuberculosis. Two other cases occurred more than 20 years after exposure and were classified as reactivation of latent M. tuberculosis infections. Mutation rates were compared between the two recently transmitted pairs versus the two latent pairs. Mean mutation rates assuming 20 hour generation times were 5.5 X 10(-10) mutations/bp/generation for recently transmitted tuberculosis and 7.3 X 10(-11) mutations/bp/generation for latent tuberculosis. Generation time versus mutation rate curves were also significantly higher for recently transmitted tuberculosis across all replication rates (p = 0.006). Assuming identical replication and mutation rates among all isolates in the final two years before disease reactivation, the u 20 hr mutation rate attributable to the remaining latent period was 1.6 × 10(-11) mutations/bp/generation, or approximately 30 fold less than that calculated during the two years immediately before disease. Mutations attributable to oxidative stress as might be caused by bacterial exposure to the host immune system were not increased in latent infections. In conclusion, we did not find any evidence to suggest elevated mutation rates during tuberculosis latency in humans, unlike the situation in rhesus macaques.

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• Antituberculosis thiophenes define a requirement for Pks13 in mycolic acid biosynthesis

  Nature Chemical Biology · 2013-06-16 · 161 citations

  articleOpen access
  PublisherOA PDFDOI

• The Structure of the Oligomerization Domain of Lsr2 from Mycobacterium tuberculosis Reveals a Mechanism for Chromosome Organization and Protection

  PLoS ONE · 2012-06-13 · 59 citations

  articleOpen access

  Lsr2 is a small DNA-binding protein present in mycobacteria and related actinobacteria that regulates gene expression and influences the organization of bacterial chromatin. Lsr2 is a dimer that binds to AT-rich regions of chromosomal DNA and physically protects DNA from damage by reactive oxygen intermediates (ROI). A recent structure of the C-terminal DNA-binding domain of Lsr2 provides a rationale for its interaction with the minor groove of DNA, its preference for AT-rich tracts, and its similarity to other bacterial nucleoid-associated DNA-binding domains. In contrast, the details of Lsr2 dimerization (and oligomerization) via its N-terminal domain, and the mechanism of Lsr2-mediated chromosomal cross-linking and protection is unknown. We have solved the structure of the N-terminal domain of Lsr2 (N-Lsr2) at 1.73 Å resolution using crystallographic ab initio approaches. The structure shows an intimate dimer of two ß-ß-a motifs with no close homologues in the structural databases. The organization of individual N-Lsr2 dimers in the crystal also reveals a mechanism for oligomerization. Proteolytic removal of three N-terminal residues from Lsr2 results in the formation of an anti-parallel β-sheet between neighboring molecules and the formation of linear chains of N-Lsr2. Oligomerization can be artificially induced using low concentrations of trypsin and the arrangement of N-Lsr2 into long chains is observed in both monoclinic and hexagonal crystallographic space groups. In solution, oligomerization of N-Lsr2 is also observed following treatment with trypsin. A change in chromosomal topology after the addition of trypsin to full-length Lsr2-DNA complexes and protection of DNA towards DNAse digestion can be observed using electron microscopy and electrophoresis. These results suggest a mechanism for oligomerization of Lsr2 via protease-activation leading to chromosome compaction and protection, and concomitant down-regulation of large numbers of genes. This mechanism is likely to be relevant under conditions of stress where cellular proteases are known to be upregulated.

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Frequent coauthors

• David Alland

  Rutgers, The State University of New Jersey

  43 shared

• Manzour Hernando Hazbón

  American Type Culture Collection

  27 shared

• William R. Jacobs

  Albert Einstein College of Medicine

  16 shared

• Maria Laura Gennaro

  Rutgers New Jersey Medical School

  14 shared

• Mandira Varma‐Basil

  12 shared

• Catherine Vilchèze

  Albert Einstein College of Medicine

  12 shared

• Konstantin P. Lyashchenko

  Chembio (United States)

  11 shared

• Danica Helb

  Rutgers New Jersey Medical School

  8 shared

Education

• Ph.D., Microbiology and Infectious Diseases

  La Sapienza University

  1993

• B.S.

  Instituto Tecnico Industriale L. Lagrange

  1985