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Rahul M. Kohli, MD, PhD

Rahul M. Kohli, MD, PhD Physician

Assistant Professor of Medicine
Assistant Professor of Biochemistry and Biophysics
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Dr. Kohli is a Penn Medicine employed physician.

Clinical Specialties

Specialty:

  • Infectious Diseases

Programs & Centers:

Board Certification:

  • Infectious Disease, 2009
  • Internal Medicine, 2007

Clinical Expertise:

  • HIV and AIDS

Description of Clinical Expertise

HIV Clinical Care; General Infectious Diseases

Practice Locations and Appointments

  • Infectious Diseases

    Perelman Center for Advanced Medicine South Pavilion, 4th Floor 3400 Civic Center Boulevard Philadelphia, PA 19104 800-789-PENN (7366)

    A facility of the Hospital of the University of Pennsylvania

Insurance Accepted

  • Aetna US Healthcare
  • Cigna
  • Cigna HealthSpring
  • CVS Health
  • Devon Health Services (Americare)
  • Gateway Health Plan
  • Geisinger Health Plan
  • HealthAmerica / HealthAssurance, a Coventry Plan
  • HealthPartners
  • HealthPartners Medicare
  • HealthSmart
  • Highmark Blue Shield
  • Horizon Blue Cross Blue Shield of New Jersey
  • Humana / Choicecare
  • Independence Blue Cross (Keystone East)
  • Intergroup
  • Keystone First
  • Multiplan
  • NJ Medicaid
  • NJ Qualcare
  • Oxford Health Plan
  • PA Medicaid
  • PA Medicare
  • Preferred Health Care/LGH
  • Rail Road Medicare / Palmetto GBA
  • Remedy Partners at Penn Medicine
  • Tricare
  • United Healthcare
  • UnitedHealthcare Community Plan
  • US Family Health Plan

Education and Training

Medical School: Harvard Medical School
Residency: Hospital of the University of Pennsylvania
Fellowship: Johns Hopkins Hospital

Memberships

American Association for the Advancement of Science, National American Chemical Society, National Infectious Disease Society of America, National

Hospital Affiliation

Dr. Kohli is a Penn Medicine employed physician.

Hospital Privileges:

  • Hospital of the University of Pennsylvania: Has privileges to treat patients in the hospital.

Research

Description of Research Expertise:

Our laboratory broadly focuses on DNA modifying enzymes and pathways, particularly those that contribute to genomic plasticity. We utilize a broad array of approaches, including biochemical characterization of enzyme mechanisms, chemical synthesis of enzyme probes, and biological assays spanning immunology and virology to study the fundamental question of how a genomic diversity arises in nature.

Mutation and modification of the genome play an important role in several physiologically relevant areas and our areas of interest include:

1. Decipher the molecular basis for deamination by AID/APOBEC enzymes and perturb deaminase immunological functions

From the host immune perspective, the generation of genomic diversity is used as both a defensive and an offensive weapon. Host mutator enzymes such as Activation-Induced Cytidine Deaminase (AID) seed diversity in the adaptive immune system by introducing targeted mutations into the immunoglobulin locus that result in antibody maturation. Related deaminases of the innate immune system can directly attack retroviral threats by garbling the pathogen genome through mutation, as accomplished by the deaminase APOBEC3G, which restricts infection with HIV. Immune mutator enzymes, however, also pose a risk to the host, as overexpression or dysregulation have been associated with oncogenesis.

2. Explore the interplay of cytosine modifying enzymes on DNA demethylation

The singular genome is responsible for a wealth of different cell types, each of which can respond and adapt to environmental cues. In part, these epigenetic differences are linked to DNA modification. These modifications center around cytosine, where DNA deamination (AID/APOBEC enzymes) , oxidation (TET family enzymes) and methylation (DNMTs) can all interplay and tune the genome's potential. We are interested in the enzymatic activities of these cytosine modifying enzymes, particularly in the process of DNA demethylation which plays a role in embryogenesis, gene regulation and a potential pathological role in cancer.

3. Target pathogen pathways that promote evolution and resistance.

From the pathogen perspective, alteration in key antigenic determinants at a rate that outpaces immune responses is a potent means for evasion. Further, rapid mutation may allow for the development of resistance to antimicrobials. In bacteria, adaptation and evolution are closely linked to the stress response of SOS pathway. The SOS pathway can be triggered by numerous stressors, including antibiotics, and the net result is accelerated acquisition of drug resistance. We aim to characterize the key regulatory and effector enzymes from the SOS pathway and to target the pathway as a means to combat antibiotic resistance.

Our research program aims to understand these pathways of purposeful DNA modification and mutation. Additionally, we apply chemical biology to decipher and target these pathways, to impede the development of multidrug-resistance in pathogens or prevent the neoplastic transformations that can result from genomic mutation.

Selected Publications:

Culyba MJ, Mo CY, Kohli RM.: Targets for Combating the Evolution of Acquired Antibiotic Resistance. Biochemistry 54 : 3573-82,2015.

Mo CY, Birdwell LD, Kohli RM.: Specificity Determinants for Autoproteolysis of LexA, a Key Regulator of Bacterial SOS Mutagenesis. Biochemistry 53 : 3158-68,2014.

Kohli RM, Zhang Y: TET enzymes, TDG and the Dynamics of DNA Demethylation Nature 502 : 472-9,2013.

Nabel CS, Lee JW, Wang LC, Kohli RM: Nucleic acid determinants for selective deamination of DNA over RNA by activation-induced deaminase Proc Natl Acad Sci USA 110 (35): 14225-30,2013.

Nabel CS, Manning SA, Kohli RM: The Curious Chemical Biology of Cytosine: Deamination, Methylation and Oxidation as Modulators of Genomic Potential ACS Chemical Biology 7 (1): 20-30,2012.

Nabel CS, Jia H, Ye Y, Shen L, Goldschmidt HL, Stivers JT, Zhang Y, Kohli RM.: AID/APOBEC deaminases disfavor modified cytosines implicated in DNA demethylation. Nature Chem Biol 8 (9): 751-758,2012.

Nabel CS, Kohli RM: Demystifying DNA Demethylation Science 333 : 1229-1230,2011.

Kohli RM: The Chemistry of a Dynamic Genome Nature Chem Biol 6 (12): 866-868,2010.

Kohli RM, Burke MD, Tao J, Walsh CT: Chemoenzymatic route to macrocyclic hybrid peptide/polyketide-like molecules J Am Chem Soc 125 : 7160-7161,2003.

Kohli RM, Walsh CT, Burkart MD: Biomimetic synthesis and optimization of cyclic peptide antibiotics Nature 418 : 658-661,2002.

View all publications

Academic Contact Info

502B Johnson Pavilion
Division of Infectious Disease, Department of Medicine
3610 Hamilton Walk

Philadelphia, PA 19104-6073
Phone: (215) 573-7523
Fax: (215) 349-5111
Patient appointments: 800-789-PENN (7366)

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